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This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 12.0-999.0, Leishmaniasis, Cutaneous Leishmania Braziliensis Complex Leishmaniasis, American Leishmaniasis; American, Cutaneous Gender: Male or female Age: >12 yrs of age Presentation: 1-to-2 ulcerative lesions, each < 30 mm in largest diameter and with a total lesion area <900 mm2 Parasitology: Parasitological confirmation of the lesion will be made by visualization or culture of Leishmania from the biopsy or aspirate of the lesion Previous treatment for leishmaniasis with Sb, pentamidine, amphotericin B, miltefosine, imidazoles, allopurinol in the last 3 months Other diseases that would be likely in the PI's opinion to interact, either positively or negatively, with treatment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Hepatitis B， Chronic Patients with chronic HBV infection (defined as HBsAg positive for at least 6 months) Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and/or hepatitis D virus (HDV) History of liver transplantation History of hepatocellular carcinoma (HCC) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-65.0, B-cell Non-Hodgkin's Lymphoma Diagnosed as B-cell Non-Hodgkin's Lymphoma (NHL) according to "2008 WHO classification of tumors of haematopoietic and lymphoid tissues", including Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, transformed indolent lymphoma, and other subtypes that investigators consider to be appropriate to be enrolled; 2. Patients must have received at least one systemic treatment (including chemotherapy), but did not achieve remission or had relapse after remission; 3. At least one measurable lesion; 4. Age18-65 years, male or female; ECOG performance status 0-1; 5. Without bone marrow involvement. Blood routine test: absolute neutrophil count ≥1.5 × 109/L, platelet ≥100 × 109/L, Hb ≥ 90g/L;. 6. Life expectancy no less than 3 months; 7. Not received chemotherapy, targeted medicine or stem cell transplantation 4 weeks before enrollment; 8. Patients have signed the Informed Consent Form. - Women during pregnancy or lactation, or fertile women unwilling to take contraceptive measures. 2. QTc elongation with clinical significance ( male˃ 450ms, female˃ 470ms), ventricular tachycardia, atrial fibrillation, cardiac conducting blockage, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease that requires treatment; 3. pericardial effusion ≥10mm sum of echo-free spaces by echocardiography; 4. Patients have undergone organ transplantation; 5. Patients received symptomatic treatment for bone marrow toxicity within 7 days prior to enrollment. 6. Patients with active hemorrhage. 7. Patients with history of thrombosis, embolism, cerebral hemorrhage, or cerebral infarction. 8. Patients with active infection, or with continuous fever within 14 days prior to enrollment. 9. Patients with active infection of HBV, HCV or HIV; 10. Had major organ surgery within 6 weeks prior to enrollment. 11. Impaired liver function ( Total bilirubin ˃ 1.5 times of normal maximum, ALT/AST˃ 2.5 times of normal maximum, for patients with infiltrative liver disease ALT/AST ˃ 5 times of normal maximum), impaired renal function (serum creatinin˃ 1.5 times of normal maximum). 12. Patients with mental disorders or those do not have the ability to consent. 13. Patients with drug abuse, long term alcoholism that may impact the results of the trial. 14. Patients who have central nervous system involvements; 15. Non-appropriate patients for the trial according to the judgment of the investigators. - | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-76.0, Metastatic Colorectal Cancer Performance status ECOG-WHO 0 or 1 Histologically proved metastatic colorectal adenocarcinoma, with non-resectable metastases Adequate hematological, hepatic, and renal functions Signed written informed consent Previous treatment (chemotherapy, targeted therapy, surgery) for metastatic disease History of autoimmune disease Acute infectious disease Known hypersensitivity grade 3-4 or contraindication to any of the study drugs Patient with any medical or psychiatric condition or disease which would make the patient inappropriate for entry into this study Bevacizumab contraindication Brain metastases Other malignancy within the last 2 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer Pregnancy, breast-feeding or absence of adequate contraception for fertile patients Patient under guardianship, curator or under the protection of justice | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Hematopoietic/Lymphoid Cancer Richter's Transformation Patients with previously treated CLL and biopsy-proven Richter's transformation with DLBCL histology according to IWCLL (Richter Transformation RT) and CD19 positive by flow cytometry OR immunohistochemistry. 2. Eastern Co-operative Oncology Group (ECOG) performance status < or =2. 3. Age > or =18 years at the time of informed consent. 4. Able to provide informed consent and be willing to participate in study schedule and events Other active malignancy receiving systemic therapy. 2. History or presence of clinically relevant disorder affecting the CNS such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis, with the exception of a history of CNS lymphoma that is controlled with intrathecal therapy. 3. Known active DLBCL in the CNS (confirmed by CSF analysis). 4. Current autoimmune disease requiring >/= 20mg/day of prednisone or systemic immunosuppressive therapy (eg. with cyclosporine or azathioprine). 5. Allogeneic HSCT within 24 weeks before the start of protocol-specified therapy. 6. Active Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg active chronic GvHD requiring systemic treatment or requirement for GvHD prophylaxis with cyclosporine or tacrolimus. 7. Cancer chemotherapy within 2 weeks before start of protocol-specified therapy, with the exception of intrathecal chemotherapy, dexamethasone, and oral small molecule inhibitors such as BTK-inhibitor, PI3K-inhibitor, or Bcl-2-inhibitor, which are allowed until the start of protocol-specified therapy). In addition, any subject whose organ toxicity (excluding hematologic) from prior treatment has not resolved to no more than CTCAE grade 1. 8. Radiotherapy within 2 weeks before the start of protocol-specified therapy. 9. Abnormal screening laboratory values as defined as following: a) ALT (SGOT) and/or ALT (SGPT) and/or ALP > or =5 x upper limit of normal (ULN); b) Total bilirubin > or = 1.5 x ULN, unless due to Gilbert's disease; c) Creatinine > or = 2.0 x ULN or creatinine clearance <50 mL/min (calculated). 10. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive). 11. Patient is pregnant or breast feeding. 12. Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving protocol-specified therapy and for an additional 24 hours after the last dose of protocol-specified therapy. 13. Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving protocol-specified therapy and for at least an additional 24 hours after the last dose of protocol-specified therapy. 14. Male who has a pregnant partner, and is not willing to use a condom during sexual activity while receiving protocol-specified therapy and for 3 months after the last dose of protocol-specified therapy. 15. Currently receiving treatment in another investigational device or drug study. 16. Subject previously treated with blinatumomab. 17. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Principal Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Non Hodgkin Lymphoma Follicular Lymphoma Indolent Lymphoma B-cell Lymphoma Transformed Lymphoma Marginal Zone Lymphoma Waldenstrom Macroglobulinemia Small Lymphocytic Lymphoma Lymphoplasmacytic Lymphoma Histologically documented (by HPI or pathology report) iNHL as defined by follicular lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma/Waldenstrom disease (LPL/WM) and small lymphocytic lymphoma (SLL) or tiNHL as defined by large B cell transformation of any of the above entities including chronic lymphocytic leukemia (CLL) 2. Patients must be eligible to undergo high dose chemotherapy (HDT) followed by ASCT as a form of remission consolidation 3. Patients without evidence of documented disease progression clinically or radiographically after ASCT (stable disease (SD), partial remission (PR) or complete remission (CR)) who have had count recovery (ANC > 500, non-transfused platelet count > 20,000) and are at least 30 days post ASCT but no more than 120 days post ASCT 4. Patients may have received any prior therapy deemed necessary for them to be eligible to HDT/ASCT except for patients whom have progressed while on Zydelig. Patients who have responded to Zydelig previously are eligible for enrollment on the protocol. 5. Age >18 6. ECOG performance status <4 7. Life expectancy of greater than four months. 8. Patients must have normal organ function as defined below (after the HDT/ASCT) total bilirubin less than 2x institutional upper limit of normal AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal Creatinine < 1.5x institutional upper limit of normal OR creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels > 1.5x upper limit of normal. 9. Because the effects of Zydelig on the developing human fetus are unknown, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Participants must agree to use contraception for at least 30 days after the last dose of Zydelig. Women of childbearing potential is defined as women who continues to have menstrual periods, have not had a tubal ligation, or the removal of fallopian tubes, ovaries or uterus. 10. Ability to understand English and the willingness to sign a written informed consent document Patients who have had chemotherapy or radiotherapy within 2 weeks of first dose of Zydelig. 2. Patients receiving any other investigational agents within 30 days of receiving Zydelig 3. Patients who were previously exposed to Zydelig and experienced progression of disease. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Zydelig. 5. Patients with active and/or untreated CNS lymphoma will not be eligible. 6. Patients with inflammatory bowel disease. 7. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (defined as requiring systemic antibiotic treatment and fever within 48 hours of screening), symptomatic congestive heart failure (patients with NYHA score of III and above are excluded), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 8. Women who are pregnant or nursing or plan to become pregnant or nurse during the course of the study. 9. Positive HIV status. 10. Patients with lack of count recovery as defined in Protocol 3.1.1.1.1. 11. Patients who are unable to swallow pills. 12. Patients with moderate to severe lung disease including Patients requiring O2 supplementation Patients unable to walk 50 feet without stopping to rest Moderate to severe obstructive or restrictive disease of the lung 13. Patients taking strong CYP3A4 inhibitors or inducers with Risk X (Avoid Combination) according to Lexicomp. Please see appendix C of the protocol for more information. 14. Patients with active hepatic disease, liver cirrhosis, or known HBV/HCV infection. 15. Patients with de novo diffuse large B-cell lymphoma. 16. Patients with h/o PCP pneumonia or CMV infection | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Diffuse Large B Cell Lymphoma Key 1. Histologically confirmed non-germinal center diffuse large B cell lymphoma (DLBCL), by immunohistochemistry using the Hans algorithm, 1. CD10 and BCL6-, 2. CD10-, BCL6+, but MUM1+ 2. Men and women ≥ 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 4. Measurable disease is defined as at least 1 lymph node >1.5 cm in longest diameter and measurable in 2 perpendicular dimensions. 5. All participants must provide fresh tumor biopsy or recent tumor tissue samples (within 2 years of study entry [informed consent form signed]). 6. Received at least one prior therapy for DLBCL that includes anthracycline based chemotherapy. 7. Participant not eligible for or refuses intensive chemotherapy and hematopoietic stem cell transplant. 8. Documented failure to achieve at least partial response (PR) with, or documented disease progression after response to, the most recent treatment regimen. 9. Neutrophils ≥ 1 x 109/L independent of growth factor support within 7 days of study entry. 10. Platelets ≥ 75 x 109/L, independent of growth factor support or transfusion within 7 days of study entry 11. Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate [eGFR]. 12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN. 13. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome), then up to 5xULN allowed. 14. Independent of erythropoietin (EPO) support or transfusion within 7 days of first dose of study drug. 15. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN. 16. Participants may be enrolled who relapse after autologous stem cell transplant if they are at least 6 months after transplant, participants should have no active infections (ie, fungal or viral). 17. Females of childbearing potential must agree to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Highly effective forms of birth control can be defined as abstinence, hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months, intrauterine contraception, hormonal methods such as contraceptive injection, oral contraceptive, etc. Males must have undergone sterilization-vasectomy, or utilize a barrier method where the female partner utilizes the effective forms of birth control noted above. 18. Life expectancy of > 3 months. 19. Able to provide written informed consent and can understand and comply with the requirements of the study. Key Current or history of central nervous system (CNS) lymphoma. 2. Prior exposure to a BTK inhibitor. 3. Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, or antibody based therapies or Chinese anti-cancer herbal therapies within 4 weeks of the start of study drug. 4. Major surgery within 4 weeks of screening. 5. Toxicity of ≥ Grade 2 from prior anti-cancer therapy (except for alopecia, absolute neutrophil count (ANC) and platelets. For ANC and platelets, please follow #9 [neutrophils] and #10 [platelets]). 6. History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent. 7. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification, or history of myocardial infarction within 6 months of screening. Left Ventricular Ejection Fraction (LVEF) is lower than 50% measured by echocardiography (ECHO) (AHA,2016). 8. QTcF (Fredericia's correction) > 450 msecs or other significant ECG abnormalities including second degree atrioventricular (AV) block Type II, or third degree AV block. 9. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. 10. Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy. 11. Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction [PCR]). 12. Pregnant or lactating women. 13. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, or put the study at risk. 14. On medications which are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or CYP3A inducers NOTE: Other protocol defined Inclusion/ | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-80.0, Richter Syndrome confirmed Richter's transformation in treatment naïve and previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma patients may have had prior exposure to ibrutinib and other B-cell signaling receptor agents Adequate hematologic function Adequate liver and kidney function Willing and able to participate in all required evaluations and procedures in this study protocol Female subjects of childbearing potential must not be pregnant upon study entry Male and female subjects who agree to use highly effective methods of birth control known allergy to any of medications chemotherapy taken within 21 days of study treatment targeted therapy within 10 days of study treatment BCR inhibitors within 24 hours of study treatment major surgery within 4 weeks of first dose of study treatment women who are pregnant known infection with HIV or Hepatitis C Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 21.0-75.0, Hepatic Encephalopathy Cirrhosis, Liver 75 years of age Cirrhosis diagnosed by either of the following in a patient with chronic liver disease (a) Liver Biopsy (b) Radiologic evidence of varices, cirrhosis or portal hypertension (c) Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1 (d) Endoscopic evidence of varices or portal gastropathy At least two HE episodes, one within the last year but not within the last month (patient can be on lactulose and rifaximin) Able to give written, informed consent (mini-mental status exam>25 at the time of consenting) Disease-related: (1) MELD score>17 (2) WBC count<1000 (3) TIPS, non-elective hospitalization or HE within last month (4) on dialysis (5) known untreated, in-situ luminal GI cancers (6) chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease or microscopic colitis, eosinophilic gastroenteritis and celiac disease) Endoscopy-related: (1) Platelet count<50,000 (2) adverse reactions to sedation (3) lack of driver or other contra-indications Safety-related: (1) Dysphagia (2) History of aspiration, gastroparesis, intestinal obstruction (3) Ongoing absorbable antibiotic use (4) Severe anaphylactic food allergy (5) allergy to ingredients Generally Recognized As Safe in the G3 capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil) (6) Adverse event attributable to prior FMT (7) ASA Class IV or V (8) Pregnant or nursing patients (9) acute illness or fever on the day of planned FMT | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Chronic Lymphocytic Leukemia Richter's Transformation Have documented CLL according to iwCLL 2. a) CLL requiring transplant according to the consensus statement 2014 Non-response or early relapse within 24 months after purine analogue combination therapy or treatment of similar efficacy plus high risk CLL TP53 deletion/mutation (del 17p-) and/or del 11 plus response to kinase inhibitors or other small molecules or Non-response or early relapse within 24 months after purine analogue combination therapy or treatment of similar efficacy and refractory to or non-tolerating kinase inhibitors or other small molecules or b) Transformation of CLL to aggressive NHL (Richter's transformation) The CLL patients should have at least one therapy with the newer targeted agents such as BCL-2 inhibitors or BCR targeting agents. Both poor risk CLL patients and patients with Richter's transformation should achieve the best possible response defined as disease sensitivity measured as CR, PR or SD prior to transplant with an available salvage therapy 3. Availability of a suitable fully matched (10/10) sibling or unrelated donor 4. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1. 5. Hematology values within the following limits unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g. myelodysplastic syndrome 2, hypoplastic bone marrow) Absolute neutrophil count ≥ 1.0 x 109/L Platelets ≥ 50 x 109/L and more than 7 days since last transfusion 6. Adequate liver function as indicated by a total bilirubin AST, and ALT ≤1.5 the institutional ULN value, unless directly attributable to the patient's CLL 7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 1 year after last dosage of obinutuzumab), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration 8. 18 years of age or older but not older then 70 years 9. Able and willing to provide written informed consent and to comply with the study protocol procedures 10. Patient agrees to inform other physicians about study participation Previous allogeneic stem cell transplant 2. Known central nervous system (CNS) involvement 3. Patients with a history of confirmed PML 4. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (left ventricular ejection fraction < 50%). 5. Organ dysfunction DLCO < 50%, TLC < 70%, FEV1 < 70% and or receiving supplementary oxygen, Inadequate renal function: Creatinine clearance < 50ml/min 6. Patients with active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral infection and active fungal infections with radiological progression despite treatment with Ambisome or active Triazole for more than a month 7. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products 8. Hypersensitivity to obinutuzumab or to any of the excipients such as for example Mannitol 9. Hypersensitivity to Fludarabine or hypersensitivity to both Treosulphan and Busulphan or any of the excipients of the used products 10. Hypersensitivity to both Ciclosporin A and calcineurin inhibitors or hypersensitivity to Mycophenolat-Mofetil or any of the excipients of the used products 11. Uncontrolled haemolytic anemia 12. Participation in another experimental drug trial (including chemotherapy, antibody treatment, kinase inhibitors, BCL2-antagonists or immunmodulatory agents) with start of the conditioning regimen/first obinutuzumab application. 13. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 14 days before start of treatment) 14. Fertile men or women of childbearing potential unless Surgically sterile or ≥ 2 years after the onset of menopause Willing to use two methods of reliable contraception including one highly effective (Pearl Index < 1) such as oral hormonal contraceptives, intrauterine device, sexual abstinence and one additional effective (barrier) while on study and maintained for up to 3 years after allogeneic transplantation or 18 months after the last dose of obinutuzumab therapy, whichever is longer 15. Vaccination with a live vaccine a minimum of 28 days prior to randomization 16. Prisoners or patients who are institutionalized by regulatory or court order or persons who are in dependence to the sponsor or an investigator | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Hepatitis C Age > 18 years, male or female 2. Willing and able to comply with program assessment, including routine tests, attendance for follow up and compliance with medicine taking. 3. Able to provide written agreement (or witnessed in the case of patients who cannot read and write) 4. Have a diagnosis of hepatitis C (based on a hepatitis C point-of-care test and then confirmed by PCR) with or without HIV Additional for PK sub-study 1. HIV well-controlled on current therapy (co-infected patients only) 2. Willing and able to comply with the additional blood sampling in the PK-PD sub-study protocol for the duration of the study Current pregnancy (pregnancy test to be performed in women of child-bearing age) 2. Previous HCV therapy. 3. HCV PCR negative 4. Patients with significant renal impairment with Cr Cl < 50 ml/min. 5. Known hypersensitivity to any part of the drug regime. 6. Presence of significant comorbidity with life expectancy of less than 12 months. 7. Clinical evidence of decompensated cirrhosis with current or previous episode of ascites, variceal bleed, encephalopathy, and treated hepatocellular cancer (HCC) [Child-Pugh score B or C]. 8. Presence of concomitant medical or social situation that would make it difficult for the patient to comply with program protocol or put the patient at additional risk 9. Concomitant medications that cause unacceptable drug-drug interactions. Additional for PK sub-study 1. Anaemia (Hb <100 mg/L) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymphoma, B-Cell Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia Waldenstrom Macroglobulinemia Mantle Cell Lymphoma Diffuse Large B Cell Lymphoma Richter's Transformation Follicular Lymphoma Marginal Zone Lymphoma Each prospective subject must meet ALL of the following in order to be eligible for this study: 1. Signed written informed consent granted prior to initiation of any study-specific procedures. 2. 18 years of age and older. 3. For the dose escalation cohorts, relapsed or refractory subjects with a diagnosis of B-cell NHL, CLL/SLL and WM who have received at least two prior systemic therapies . Subjects must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens. Subjects with low grade lymphoma must be progressing and requiring treatment.. 4. For the expansion cohorts, the following must be met Cohort A: Relapsed/Refractory (R/R) CLL/SLL subjects with at least 2 prior systemic therapies and previously treated with a covalent BTKi who must have a documented BTK mutation on C481 residue Cohort B: R/R CLL/SLL subjects who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue. In this study, intolerance to standard therapy is defined as having experienced a grade 3 or higher adverse event that was caused by the standard therapy and resulted in treatment discontinuation Cohort C: Richter's transformation subjects who have failed at least one prior therapy Cohort D: Follicular Lymphoma (FL) subjects who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A Cohort E: Mantle Cell Lymphoma (MCL) subjects who have failed at least 2 prior systemic therapies Cohort F: Marginal Zone Lymphoma (MZL) subjects who have failed at least 2 prior systemic therapies Cohort G: High-grade B-cell lymphoma subjects who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations Cohort H: Waldenström macroglobulinemia (WM) subjects who have failed at least 2 prior systemic therapies 5. Disease status requirement: 1. For CLL subjects, symptomatic disease that mandates treatment (Hallek et al. 2018). 2. For B-cell NHL subjects, measurable disease by imaging scan. 3. For WM, serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the upper limit of normal (ULN). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 7. Good organ function 1. Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation or by 24-hour urine collection. 2. Total bilirubin ≤ 1.5 x institutional ULN (total bilirubin of ≤ 3 x institutional ULN in subjects with documented Gilbert's syndrome). 3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN. 4. Platelet count ≥ 50,000/µL 5. Absolute neutrophil count (ANC) ≥ 1000/µL. 6. Hemoglobin (Hgb) ≥ 8.0 g/dL, stable for ≥ 1 week. 8. For men and women of child-bearing potential, willing to use adequate contraception (e.g., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study. 9. Female subjects of child-bearing potential must have a negative serum pregnancy test within 14 days of the first day of drug dosing. 10. Ability to swallow oral medications without difficulty Potential subjects who meet ANY of the following are not eligible for enrollment into this study: 11. Had immunotherapy, radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 5 half-lives or four weeks (whichever is shorter) prior to treatment initiation, or oral therapy within 5 half-lives or one week (whichever is shorter) prior to treatment initiation. 12. Transformation of FL to a more aggressive subtype of lymphoma or grade 3b FL 13. Subjects currently being treated with the following drugs: 1. CYP 2C9 substrates with a narrow therapeutic index (such as warfarin, phenytoin) 2. CYP 2C8 substrates with a narrow therapeutic index (such as paclitaxel) 3. CYP 2C19 substrates with a narrow therapeutic index (such as S-mephenytoin) 4. CYP 2D6 substrates with a narrow therapeutic index (such as thioridazine, pimozide) 5. P-gp substrates with a narrow therapeutic index (such as digoxin) Note: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a subject to be eligible for study enrollment. 14. Prior allogeneic bone marrow transplant. 15. Active central nervous system (CNS) involvement. 16. Pregnant or breast-feeding women. 17. Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug. 18. Uncontrolled illness including but not limited to ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, cardiac infarction in the past six months, and psychiatric illness that would limit compliance with study requirements. 19. QTc prolongation (defined as a QTc > 450 msecs) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation. 20. Active human immunodeficiency virus (HIV) infection, Hepatitis B, or Hepatitis C infection. 21. Other medical or psychiatric illness or organ dysfunction which, in the opinion of the Investigator, would either compromise the subject's safety or interfere with the evaluation of the safety of the study agent. 22. History of prior cancer within < 1 year, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Arthroplasty Complications Inflammatory Response end stage knee OA necessitating TKR surgeries autoimmune diseases, malignancies, previous knee surgery or post-traumatic arthritis | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Cervical Cancer Age : 18-70 years old; 2. Histology or cytology confirmed cervical squamous cell carcinomas; 3. 2009 FIGO stage includesⅠB2, ⅡA2, ⅡB-ⅣA; 4. Performance status(PS): 0-1; 5. Peripheral blood meet the following conditions: neutrophil count > 2.0 * 109/L, white blood cell count > 4.0 * 109/L, the platelet count > 100.0 * 109/L; 6. Liver and kidney function meet the following conditions: bilirubin < 1.5 mg/dl, AST and ALT < 2 times the upper limit of normal serum creatinine < 1.5 mg/dl, creatinine clearance > 50 ml/min; 7. Signed informed consent before treatment There is no definite pathological diagnosis; 2. Clinical or imaging examination revealed distant metastases; 3. Pelvic had received radiotherapy; 4. Patients can't attend the study because of the associated with other diseases; 5. Patients can't sign the informed consent because of mental disorders, mental disorders; 6. Uncontrolled active infection; 7. No follow-up | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Del(17P) Patients diagnosed as CLL years or older Able and willing to provide the written informed consent Younger than 18 years | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 20.0-120.0, Part1: Advanced B-cell Malignancies Part2: r/rCLL and r/rMCL Part3: Untreated CLL Key Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses Japanese subjects at least 20 years of age at the time of study entry Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of a ≥ 2.0 cm lesion as measured in the longest dimension by computerised tomography [CT] scan). Note: Not applicable to subjects with Chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM) Eastern Co-operative Oncology Group (ECOG) Performance Status (PS) of ≤ 2 Adequate organ function defined as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 × institutional upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN except in the case of subjects with documented Gilbert's disease, ≤ 2.5 × ULN Serum amylase ≤1.5 × ULN or serum lipase ≤1.5 × ULN <Part2> Relapsed or refractory CLL/SLL: Confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to ≥ 1 prior therapy for CLL/SLL, and has active disease meeting IWCLL 2008 (Hallek 2008) Relapse or refractory MCL: Confirmed diagnosis of MCL, which has relapsed after,or been refractory to ≥ 1 prior therapy for MCL, and documented failure to achieve at least PR with, or documented disease progression after, the most recent treatment regimen. <Part3> Japanese subjects: 1. ≥ 65 years of age OR 2. ≥ 20 and < 65 years of age, provided that they meet at least one of the following i. Creatinine clearance 30 to 69 mL/min using the Cockcroft-Gault equation. ii. A score higher that 6 on the Cumulative Illness Rating Scale-Geriatric History of other invasive malignancy within 2 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification (New York Heart Association Functional Classification 1994) Malabsorption syndrome, disease significantly affecting GI function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery such as gastric bypass Known CNS involvement by lymphoma/leukemia Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome (for CLL/SLL) Receipt of any biological or immunological based therapies (including experimental therapies) for leukaemia or lymphoma or myeloma (including, but not limited to, MAb therapy such as rituximab, or cancer vaccine therapies) within 4 weeks prior to the first dose of acalabrutinib Any prior therapy with BCR inhibitors (eg, BTK, PI3Kδ, or SYK inhibitors) or BCL-2 inhibitors (eg, venetoclax/ABT-199) Known history of HIV, serologic status reflecting active hepatitis B or C infection,or any uncontrolled active systemic infection History of stroke or intracranial haemorrhage within 6 months prior to first dose of study drug | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 13.0-68.0, To Compare the Effects of Mycophenolate Mofetil With Cyclophosphamide in Neplaese Lupus Nephritis Patients Newly diagnosed LN with ISN/RPS histopathology classes III to V Patients with biopsy had proven ISN / RPS classes I, II and VI LN Patients with previous history of treatment and relapse of lupus nephritis Patients who were receiving continuous dialysis for more than two weeks prior to randomization Patients of less than 12 years of age Patients who had concurrent infection or illness at the time of enrollment Patients who were taking concurrent medications which are supposed to have interactions with MMF or CYC Female patients who were pregnant and breastfeeding Patients who did not give consent for participation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Kidney Failure Dialysis Related Complication hemodialytic treatment from at least 6 months (3 times for week), blood flow rate during dialysis session (Qb) ≥250 ml/min using arterovenous fistula (AVF) or permanent central venous catheter (CVC), blood creatinine clearance <5 ml/min, urine output <500 ml/die neoplastic diseases, autoimmune diseases, solid organ or bone marrow transplantation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymphoma Non-Hodgkin Lymphoma Diffuse Large B-Cell Lymphoma Burkitt Lymphoma Patients must have histologically or cytologically confirmed B-cell lymphoma confirmed by the Laboratory of Pathology, NCI, as follows: Phase1b Aggressive B-cell lymphoma: includes DLBCL and subtypes, transformed lymphoma, Burkitt lymphoma, as well as High-grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s). -Indolent B-cell lymphoma CLL/SLL is excluded given alternative dosing of FDA-approved venetoclax for relapsed 17p CLL and increased risk of TLS with CLL/SLL compared to other non-Hodgkin lymphomas NOTE: Patients with known active CNS lymphoma are not eligible. Phase 2 Relapsed and/or refractory DLBCL and subtypes, including transformed lymphoma as well as High grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s) Relapsed and/or refractory Follicular lymphoma (FL) Untreated Mantle cell lymphoma (MCL) Relapsed and/or refractory disease on at least 1 prior treatment regimen, as follows Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anthracyclineDoxorubicin-containing regimen Indolent B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anti-CD20 antibodyRituximab-containing regimen The following restrictions apply to current or prior anti-cancer treatment, prior to the first dose of study drug Patients who are actively receiving any other investigational agents Any chemotherapy, external beam radiation therapy, or anti-cancer antibodies within 2 weeks prior to the first dose of study drug Radio or toxin-immunoconjugates within 10 weeks prior to the first dose of study drug Previous treatment with greater than one of the study agents (i.e., venetoclax, Ibrutinib or Revlimid), excluding prior prednisone or anti-CD20 antibody treatment Prior allogeneic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug Not recovered (i.e., less than or equal to Grade 1 or baseline) from adverse events due to previously administered anti-cancer treatment, surgery, or procedure. NOTE: Exceptions to this events not considered to place the subject at unacceptable risk of participation in the opinion of the PI (e.g., alopecia) Patients requiring the use of warfarin are excluded because of potential drug-drug interactions that may potentially increase the exposure of warfarin Patients requiring the following agents within 7 days prior to the first dose of venetoclax are excluded | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia in Relapse Chronic Lymphocytic Leukemia in Remission Documented CLL or SLL requiring treatment according to IWCLL after either being refractory to first line therapy or relapse after initial therapy Age at least 18 years Adequate bone marrow function defined as Absolute neutrophil count (ANC) >0.75 x 109/L Platelet count >30,000 /μL 30 x 109/L Hemoglobin >8.0 g/dL (5 mmol/L) Unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy Creatinine clearance (CrCL) ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection Adequate liver function as indicated Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN) Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin) Any prior therapy with ibrutinib and/or venetoclax Transformation of CLL (Richter's transformation) Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML) Malignancies other than CLL currently requiring systemic therapies or not being treated in curative intention before or showing signs of progression after curative treatment Known allergy to xanthine oxidase inhibitors and/or rasburicase Known bleeding disorders (e.g., von Willebrand's disease or hemophilia) Uncontrolled or active infection Patients requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor (see appendix K). or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists. Please note: Patients being treated with NOACs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib History of stroke or intracranial hemorrhage within 6 months prior to registration Major surgery within 28 days prior to registration | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Benign Paroxysmal Positional Vertigo patients who have had symptoms of vertigo for at least 1 week duration patients with a documented positive Dix-Hallpike test on referral patients with intact cognitive function and had the ability to communicate and understand instructions to perform a home-based exercise patients with history of prior ear surgery patients with orthopaedic or connective tissue disorder that impairs functional neck or trunk range of motion patients with a significant neurological disorder or spinal cord damage, and patients who have been prescribed with home-based exercises for BPPV | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Intrathoracic Lymphadenopathy Indication to sampling of intrathoracic lymphadenopathy based on computed tomography (CT) and/or positron emission tomography (PET)/CT findings Signed informed consent High risk conditions for the performance of bronchoscopy and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) High risk condition for deep sedation (ASA 4) Pregnancy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, B Acute Lymphoblastic Leukemia CD19 Positive Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly Minimal Residual Disease Philadelphia Chromosome Positive Recurrent Diffuse Large B-Cell Lymphoma Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma T-Cell/Histiocyte-Rich Large B-Cell Lymphoma For diffuse large B-cell lymphoma (DLBCL) Histologically confirmed aggressive B cell non-Hodgkin lymphoma (NHL) including the following types defined by World Health Organization (WHO) 2008 DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR Primary mediastinal (thymic) large B cell lymphoma Transformation of follicular lymphoma to DLBCL will also be included Subjects with DLBCL must have progressed, had stable disease (SD), or recurred after initial treatment regimens that an anthracycline and an anti CD20 monoclonal antibody; subjects who relapse >= 12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant For B acute lymphoblastic leukemia (ALL) Chemotherapy refractory disease in subjects with B-ALL is defined as progression or stable disease after two lines of standard therapies (two induction regimens), or relapsed disease after 2 established induction regimens Subjects with persistent or relapsed minimal residual disease (MRD) / next generation sequencing (NGS) relapse require verification of relapse on two occasions at least 4 weeks apart Subjects with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs) History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years History of Richter?s transformation of chronic lymphocytic leukemia (CLL) Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management; simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment; known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen [HBsAg] positive) or hepatitis C virus (anti hepatitis C virus [HCV] positive); a history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment, or have cardiac atrial or cardiac ventricular lymphoma involvement Subjects receiving anticoagulation therapy Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment History of severe immediate hypersensitivity reaction to any of the agents used in this study Women of child bearing potential who are pregnant or breastfeeding; females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential In the investigators judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 40.0-999.0, Health Status Unknown Elevated PSA Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information Note: HIPAA authorization may be included in the informed consent or obtained separately Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 3 months (93 days) prior to being registered for protocol African-American or white men (Hispanic or non-Hispanic) Prostate biopsy-naive or a single negative biopsy Having elevated prostate specific antigen (PSA) (> 2.5 ng/ml) and no palpable nodule on digital rectal exam (DRE) Ability to understand the willingness to sign a written informed consent Patients must be willing to undergo a radiologic imaging before and after biopsy of the prostate Patients must be willing to undergo a biopsy of the prostate Patients who have had chemotherapy or radiotherapy within 12 months of the study for other diagnoses not related to prostate cancer Patients receiving any other investigational agents Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with active inflammatory bowel disease Patients who are unable to undergo MRI Patients who had any surgery of the prostate including TURP (transurethral resection of the prostate) Patients who had > 1 prior prostate biopsy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Schizophrenia Spectrum and Other Psychotic Disorders he/she currently uses CLZ or he/she has used CLZ in the past/will use CLZ he/she has received a diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder NOS his/her age must be ≥18 years old he/she must be able to speak and read the language of the Informed Consent (differs per country) he/she must be mentally competent and have decisional capacity with regard to a decision to participate in the current study admission to a psychiatric unit involuntarily (not all countries) a history of Parkinson's disease | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 14.0-999.0, Non-Hodgkin Lymphoma Lymphoma Diffuse Large B-Cell Lymphoma Gray Zone Lymphoma Primary Central Nervious System Lymphoma Patients must have a diagnosis of B-cell lymphoma confirmed by Laboratory of Pathology, NCI, that is relapsed from or refractory to prior therapy as follows Cohort 1: B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (i.e., Gray-zone lymphoma or GZL) Cohort 2: Extranodal diffuse large B-cell lymphoma involving one or more of the specified extranodal sites (i.e., extranodal DLBCL). The following subtypes are included (they do not have to be confirmed as non-GCB subtype for study entry) Primary CNS lymphoma (PCNSL) Primary testicular lymphoma (PTL) Primary breast lymphoma (PBL) Primary cutaneous DLBCL, leg-type Intravascular large B-cell lymphoma (IVBCL) Diffuse large B-cell, NOS, activated B-cell type, involving 1 or more extranodal site NOTE: For GZL, diagnosis will be in accordance with the 2016 World Health Organization classification of lymphoid malignancies. Patients diagnosed with other extranodal DLBCL subtypes or that are not otherwise specified (NOS) must involved at least 1 extranodal site and must be considered non-GCB by local immunohistochemistry algorithms. Cases that are non-GCB by the Hans are considered eligible as well as cases of DLBCL that are both CD10+ and MUM1+ Evaluable disease by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on CT or MRI and/or evaluable FDG-avid lesions on PET) Patients with DLBCL who best fit the of EBV+ DLBCL, NOS are not eligible Current or prior anti-cancer treatment prior to the first dose of pembrolizumab as defined below Chemotherapy, targeted small molecule therapy, or other anti-cancer treatment not otherwise specified below within 2 weeks Radiation therapy within 2 weeks Anti-cancer monoclonal antibody (mAb) treatment within 4 weeks Use of an investigational agent (e.g., biologic, drug, or other) within 4 weeks Allogeneic stem cell transplant within 100 days Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent at any time No current use of systemic corticosteroids at physiologic doses > 10 mg/day of dexamethasone or equivalent are permitted. Patients receiving current systemic steroids must be on a stable steroid dose (i.e., less than or equal to 10 mg/day of dexamethasone or equivalent at the same dose for at least 7 days). Patients who recently discontinued systemic steroids must have completed them at least 7 days prior to entry Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Velopharyngeal Insufficiency Patients must have border line velopharyngeal abnormality which was diagnosed clinically. Ability to understand and the willingness to sign a written informed consent(if he was a child so his parents or his guardian should has tis ability) Mental Retardation. 2. Presence of Neurological deficit affecting speech. 3. Palatal paralysis or paresis. 4. Overt cleft palate | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymphoma Adult T-Cell Leukemia/Lymphoma Lymphatic Diseases Subjects must meet all of the following to participate in this study: 1. Informed consent and HIPAA authorization for release of personal health information obtained. 2. Age ≥ 18 years at the time of consent. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 4. Histological confirmation of biopsy-proven peripheral T-cell leukemia/lymphoma consistent with ATLL Included subtypes will be: acute, lymphomatous, and chronic unfavorable. Chronic unfavorable is defined as the chronic variant with at least one of the following: lactate dehydrogenase (LDH)>upper limit of normal (ULN), blood urea nitrogen (BUN)>ULN, Albumin<lower limit of normal (LLN) Positive human T-lymphotropic virus-1 (HTLV-1) antibody testing with confirmatory testing via Western blot, enzyme-linked immunosorbent assay (ELISA), or molecular testing (PCR). 5. Documented negative serologic testing for human immunodeficiency virus (HIV). 6. If positive for HBV exposure or prior infection, can continue to participate in trial with prophylactic entecavir (for HBV). If positive for hepatitis c virus (HCV) exposure or active infection, can participate in trial with monitoring for liver function abnormalities. 7. Demonstrate adequate organ function as defined below; all screening labs to be obtained within three days prior to study treatment. System: Renal -Calculated creatinine clearance Laboratory Value: ≥ 30 mL/min using the Cockcroft-Gault formula for subjects with creatinine levels > 2.0 x institutional ULN System: Hepatic Bilirubin Laboratory Value: ≤ 3.0 mg/dL System: Hepatic Aspartate aminotransferase (AST) Laboratory Value: ≤ 2.5 × ULN System: Hepatic Alanine aminotransferase (ALT) Laboratory Value: ≤ 2.5 × ULN 8. Females of childbearing potential must have a negative serum pregnancy test within three days (72 hours) prior to initiating study treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. 9. Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 24 weeks (6 months) after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets <1% failure rate for protection from pregnancy in the product label. 10. Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 24 weeks (6 months) after the last dose of study therapy. 11. As determined by the enrolling physician or protocol designee, willingness and ability of the subject to understand and comply with study procedures 12. Prior Treatment: Previously untreated or has received a maximum of one cycle of any combination chemotherapy (e.g. cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), CHOEP, DA-EPOCH, doxorubicin, cyclophosphamide, cytarabine, vincristine, methotrexate/Etoposide, ifosfamide, cytarabine, methotrexate (CODOX-M/IVAC), HyperCVAD) within 4 weeks of signing the main consent form. Additionally, a patient may have taken antiretroviral therapy (e.g. azidothymidine (AZT) and/or IFN) at any time prior to study enrollment 13. CD30 expression determined by flow cytometry or IHC. NOTE: If CD30 testing was previously done on the biopsy sample from diagnosis, this information will be collected. If CD30 testing was not done, an archival sample from the biopsy used for diagnosis will be requested and tested for CD30. CD30 testing will also be done on the bone marrow tissue collected from the bone marrow exam. If we are unable to obtain an archival sample or if the bone marrow exam is negative, a new biopsy will be performed to confirm the diagnosis and test for CD30 Subjects who meet any of the following should be excluded from study participation: 1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). 2. Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years. 3. Previous exposure to brentuximab vedotin (BV). 4. History of allergic response to BV-CHEP or its components or to any of the required prophylactic medications or reasonable alternatives. 5. Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 40%, symptomatic coronary artery disease or symptomatic arrhythmias 6. Subjects with severe hepatic insufficiency Child-Pugh Score > 6 7. Subjects with severe renal impairment (i.e., creatinine clearance ≤ 30 mL/min; see Appendix B Renal Impairment Guidelines). 8. patients with pre-existing neuropathy grade 2 or higher. 9. Patients receiving prohibited medications listed in the patient handout provided in 11.4 Appendix D: Prohibited Medications or Those to be used with Caution (ie, ketoconazole, itraconazole, ritonavir, macrolide antibiotics, erythromycin phenytoin, phenobarbital, carbamazepine, and valproic acid). 10. Patients with a parenchymal brain lesion thought to be consistent with active lymphoma on screening CT/MRI. Of note, patients with cerebrospinal fluid (CSF) involvement alone are not excluded | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Melanoma Age > 18 years 2. Primary melanoma > 1 mm in Breslow depth 3. Stage III or IV disease as determined either by sentinel node biopsy, biopsy of clinically enlarged lymph nodes, and/or imaging. If stage IV, must have tissue biopsy confirming presence of stage IV melanoma Pregnant patients 2. Contraindication to contrasted imaging (due to allergy or renal insufficiency) 3. Serum PCV <30% | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, CD20 Positive Mantle Cell Lymphoma FOR (STEP 0 Patients must have histologically confirmed mantle cell lymphoma, with documented cluster of differentiation (CD19) or CD20 expression and cyclin D1 (BCL1) by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH); the diagnosis must be confirmed by formal hematopathology review at the enrolling center, including assessment of Ki-67 proliferation index (=< 30% versus > 30% versus ?indeterminate? Ki-67 index) Patients should be deemed to be potentially eligible and willing candidates for auto-HCT by the enrolling physician Patient may be receiving or have completed induction therapy within 60 days prior to preregistration to step 0; no more than 300 days may have passed between the first day of induction therapy and preregistration to step 0 For patients who have completed induction therapy, restaging evaluation must show status of partial (PR) or complete response (CR); patients preregistered post-induction with evidence of clinical disease progression are not eligible for preregistration Up to two regimens of chemotherapy are allowed as long as a continuous response was ongoing throughout therapy NOTE: For example, a patient who started treatment with rituximab/bendamustine and was then switched to rituximab(R)-cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) (due to insufficient response or excessive toxicity) would be counted as having received 2 regimens; however, R-CHOP alternating with R-dexamethasone, high-dose cytarabine, and cisplatin (DHAP) as a planned induction regimen would count as one regimen Patient does not have any documented history of central nervous system (CNS) involvement by mantle cell lymphoma; this includes no evidence of parenchymal brain, spinal cord, or cerebrospinal fluid involvement; radiculopathy symptoms from nerve root compression by lymphoma do not constitute CNS involvement Patient must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the original diagnostic biopsy available for submission to Adaptive Biotechnologies for ClonoSEQ ID molecular marker identification of unique clonal immunoglobulin deoxyribonucleic acid (DNA) sequence NOTE: Patients for whom the molecular marker is identified will have peripheral blood collected after completion of induction (patient?s disease status is PR or CR) and submitted to Adaptive Biotechnologies for minimal residual disease (MRD) assessment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Hypersplenism All patients with documented evidence of liver cirrhosis (of any etiology other than alcoholic cirrhosis) and portal hypertension, based on clinical examination, abdominal ultrasound examination, upper gastrointestinal endoscopy Male and female patients aged between 18-60 years Patients with splenomegaly of any cause other than liver cirrhosis Patients with any lymphoproliferative disorders Patients with extrahepatic malignancy Patients younger than 18 years old Any associated cardiovascular disease Failure to obtain consent | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 19.0-999.0, Cardiovascular Diseases Neuro-Degenerative Disease Cancer Pregnancy Men and women Older than 18 years Cardiovascular disease neurodegenerative disease Cancer Pregnancy Inability to understand and to want Refusal to sign the informed consent | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-64.0, Lymphoma, Large B-Cell, Diffuse Age 18 years Histologically confirmed CD20+ DLBCL based on revised WHO 2008 Lymphoma Classification. The following subgroups and variants can be included ALK-positive large B-cell lymphoma Intravascular large B-cell lymphoma T-cell rich B-cell lymphoma Myc/BCL-2 double hit lymphoma Follicular lymphomas grade 3b DLBCL with previously undiagnosed concurrent small cell infiltration in bone marrow, lymph node, or extranodal site and lymphomas intermediate between DLBCL and Burkitt's lymphoma are allowed Posttransplantation lymphoma (PTLD), discordant or transformed lymphoma are NOT allowed Severe cardiac disease: cardiac function grade 3-4, left ventricular ejection fraction <45% Impaired bone marrow liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule (Hemoglobin < 9 g/dL, ANC < 1.5 × 109/L, Platelet count < 75 × 109/L, creatinine clearance < 40 mL/min, ALT/AST > 2.5 x ULN, bilirubin 1.5 x ULN, INR > 1.5) Pregnancy/lactation Men and women of reproductive potential not agreeing to use effective contraception during treatment and for 18 months after completion of treatment (Effective contraception is combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), hormone-releasing IUD, bilateral tubal occlusion, vasectomised partner, or sexual abstinence Patients with other severe medical problems, including active infections, cardiac or pulmonary disease, history of PML and with an expected short survival for non-lymphoma reasons Known HIV positivity Active or chronic hepatitis B virus (HBV) infection (defined as positive HBsAg serology), or active hepatitis C virus (HCV) infection (defined by antibody serology testing). HBsAg, HBcAb, and HCVAb must be tested during screening. Patients who have protective titers of HBsAb along negative HBsAg after vaccination or prior but cured hepatitis B are eligible Vaccination with a live vaccine within one month prior to randomization Patients with a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment Earlier treatment containing anthracyclines | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, B Cell Lymphoma B Cell Leukemia Myeloma Hepatocellular Carcinoma Pancreatic Carcinoma Adenocarcinoma of Esophagogastric Junction I. B-Cell Lymphoblastic Leukaemia/Lymphoma 1. Patients aged between 18 ~ 65 with B-cell lymphoblastic leukaemia/lymphoma. 2. CD19-positive B-cell lymphoblastic leukaemia/lymphoma. 3. Patients with unmet medical needs for which there are no effective therapies known at this time: A. Relapsed or Refractory (r/r) Acute Lymphoblastic Leukemia (ALL) Patients with r/r ALL for whom hematopoietic stem cell transplantation (HSCT) is not suitable due to following reasons: 1. Age; 2. Excessive tumor burden or concomitant disease; 3. No donor available. B. CD19-positive Follicular Lymphoma: 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy; 2. Less than 6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months); 3. Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.). C. Chronic Lymphocytic Leukemia (CLL) 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy); 2. Less than6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months); 3. Not eligible or appropriate for conventional HSCT. 4. Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.). D. Mantle Cell Lymphoma 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy); 2. Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.)； 3. Relapsed after prior autologous SCT. E. B-Cell Prolymphocytic Leukemia (PLL) Relapsed or residual disease after at least 1 prior therapy and not eligible for HSCT. F. CD19-positive Diffuse Large B Cell Lymphoma 1. At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy; 2. Stage III-IV disease. 3. Less than 6 months between last chemotherapy and disease progression (most recent progression free interval < 6 months); 4. Disease progression after most recent therapy (chemotherapy, MoAb, etc.). 4. Expected survival > 12 weeks. 5. At least one measurable lesion (≥ 10 mm) for patients with lymphoma. 6. ECOG scores 0-1, or KPS scores > 70. 7. Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis. 8. WBC ≥ 2.5×10^9/L; PLT ≥ 60×10^9/L (for patients with lymphoma); Hb ≥ 9.0 g/dL; LY ≥ 0.47×10^9/L; LY% ≥ 15%. 9. Serum Alb ≥ 30 g/L. 10. Serum creatinine ≤ 1.5 ULN. 11. ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN. 12. Serum total bilirubin ≤ 1.5 ULN. The above lab results should not those obtained from continuous supportive treatment that is ongoing. II. Myeloma 1. Patients aged between 18 ~ 75 with relapsed or refractory multiple myeloma. 2. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination. 3. Patients with relapsed or refractory malignancies who meet the following descriptions: 1. Curative efficacy is little or disease progressed after 2 courses of standard treatment regimen; 2. Disease relapsed after chemotherapy or HSCT. Curative efficacy is little or disease progressed after 2 courses of original treatment regimen; 3. More than 30 days between last treatment and disease progression; 4. There is no indication for HSCT at present; 5. Disease progression is defined as per "Chinese Guidelines for Diagnosis and Treatment of Multiple Myeloma (Version 2015)". One or more of the following conditions should be met: i. Serum M-protein increases ≥ 25% (absolute increase should be ≥ 5 g/L). If serum M protein is ≥ 50 g/L at baseline, increase of serum M protein can be ≥ 10 g/L; ii. Urine M-protein increases ≥ 25% (absolute increase should be ≥ 200 mg/24 h); iii. If the serum and urine M-protein are not detectable, a ≥ 25% increase in the difference between involved and uninvolved FLC levels is required (absolute increase should be ≥ 100 mg/L); iv. Bone marrow plasma cell percentage increases ≥ 25% (absolute increase should be ≥ 10%); v. Size of existing bone lesions or soft tissue plasmacytomas increased by ≥ 25%, or development of new lytic bone lesions or oft tissue plasmacytomas; vi. Development of hypercalcemia that can be attributed to plasma cell proliferative disorder (corrected calcium is > 2.8 mmol/L or 11.5 mg/dL). 4. Expected survival > 12 weeks. 5. Disease is measurable, and at least one of the following conditions should be satisfied: 1. Serum M-protein is ≥ 10 g/L; 2. 24-hour urine M-protein is ≥ 200 mg; 3. Serum FLC is ≥ 5 mg/dL; 4. Plasmacytomas that can be measured or evaluated by imaging; 5. Bone marrow plasma cell percentage is ≥ 20%. 6. ECOG scores 0 or CCI scores ≤ 2. 7. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis. 8. WBC ≥ 1.5×10^9/L; PLT ≥ 45×10^9/L; Hb ≥ 9.0 g/dL. 9. Serum creatinine ≤ 1.5 ULN. 10. ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN. The above lab results should not those obtained from continuous supportive treatment that is ongoing. III. Hepatocellular Carcinoma (HCC) 1. Patients aged 18 ~ 70 with refractory hepatocellular carcinoma. 2. Patients with HCC that cannot be eradicated by resection who have received ablation or resection in the last 4 to 12 weeks. 3. IHC testing confirmed as GPC3-positive HCC. 4. Expected survival > 12 weeks. 5. At least one measurable lesion (≥ 10 mm). 6. Cirrhosis of the liver: Child-Pugh Class A, or Child-Pugh Class B scored at 7. 7. ECOG scores 0 or KPS scores > 70. 8. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis. 9. Hematology: WBC ≥ 2.5×10^9/L; PLT ≥ 60×10^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.0×10^9/L; LY ≥ 0.4×10^9/L. 10. Blood Chemistry: Serum Alb ≥ 30 g/L; Serum lipase and serum amylase < 1.5 ULN; Serum creatinine ≤ 1.5 ULN; ALT ≤ 5 ULN; AST ≤ 5 ULN; Serum total bilirubin ≤ 2.5 ULN. 11. Coagulation Test: Prothrombin time is at most 4 seconds longer than normal value. 12. Able to understand and sign the informed consent. All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment. IV. Pancreatic Carcinoma and Adenocarcinoma of Esophagogastric Junction 1. Patients aged 18 ~ 70 with pathologically confirmed advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction. 2. IHC testing confirmed as Claudin18.2 positive. 3. Patients with advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction that cannot be eradicated by resection. 4. Expected survival after first dose of study drug > 12 weeks. 5. At least one measurable lesion (≥ 10 mm) available for imaging assessment. 6. ECOG scores 0 7. Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis. 8. WBC ≥ 2.5×10^9/L; PLT ≥ 100×10^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.5×10^9/L; LY ≥ 0.47×10^9/L; LY% ≥ 15%. 9. Serum Alb ≥ 30 g/L. 10. Serum lipase and serum amylase < 1.5 ULN. 11. Serum creatinine ≤ 1.5 ULN. 12. ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN; If osseous metastasis or liver metastasis is developed and alkaline phosphatase is > 2.5 ULN, than ALT and AST should be < 1.5 ULN. 13. Serum total bilirubin ≤ 1.5 ULN. 14. PT: INR < 1.7; PT < (ULN + 4) s All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment Patients with any of the following conditions are not eligible for this study. 1. Transduction of target lymphocytes < 10%, expansion in response to αCD3/CD28 costimulation < 5-fold. 2. Pregnant or lactating women. 3. HIV positive, or HCV positive 4. Uncontrolled active infection, including active tuberculosis and HBV DNA copies ≥ 1×10^3 copies/mL. 5. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. 6. Allergic to immunotherapies and related drugs. 7. Patients with heart disease for which treatment is needed or with poorly controlled hypertension. 8. Hyponatremia: serum sodium level < 125 mmol/L. 9. Baseline serum potassium < 3.5 mmol/L (taking potassium supplements before participating in the study to raise potassium level is acceptable). 10. Previous treatment with chemoradiotherapy, immunotherapy and tumor-targeting drug conducted 2 weeks prior to participation in this study or blood collection. 11. Patients have undertaken immunosuppressor for graft-versus-host disease (GVHD) within 4 weeks before participation in this study or blood collection, or the patient is diagnosed with acute or chronic GVHD. 12. Other severe disease that may restrain patients from participating in this study (e.g. diabetes, severe cardiac dysfunction, myocardial infarction or unstable arrhythmias or unstable angina in recent 6 months, gastric ulcer, active autoimmune disease, etc.) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Neoplasms, Malignant Breast Neoplasm Carcinoma, Basal Cell Carcinoma, Squamous Cell Melanoma Skin Neoplasm Head and Neck Neoplasms Subject must be capable of giving informed consent or has an acceptable surrogate capable of giving consent on behalf of the subject. 2. Subject has an eligible tumor that is within 5 mm of the surface (either skin or mucosa) or has had a tumor removed with a tumor bed that is within 5 mm of the surface. 1. Eligible tumors types Intraoral tumors: squamous cell carcinoma (SCC), melanoma Primary cutaneous tumors (including, but not limited to): SCC, basal cell carcinoma (BCC,) melanoma Breast malignancies post surgery Other tumors: any tumor within 5 mm of the surface and with planned radiation therapy Previous adverse reaction to a charcoal product e.g., a local hypersensitive response from a black tattoo or from ingestion of activated charcoal 2. Previous adverse reaction to the suspending agent 3. Subject has a pacemaker that is not known to be MRI compatible 4. Subject has a non-removable implant or device with metal that is not known to be MRI compatible 5. Subject is pregnant or has a likelihood for becoming pregnant during the basic study timeframe. Note: There is no known harm to the woman or her fetus from participating; this is precautionary only | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Renal Cell Carcinoma Histologically confirmed locally advanced or metastatic renal cell carcinoma, clear cell histology that can be considered for partial or complete nephrectomy cT1b-T2a Grade (G) 4, cT2b G3/4, c T3-cT4 any grade and any cT with cN1 or M1 disease Locally advanced disease is defined as follows Adjacent organs (T4) or vascular invasion (Level III/ IV / IVC thrombus) Bulky lymphadenopathy encasing renal or great vessels Written and voluntary informed consent Renal function (creatinine level within normal institutional limit, or creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula) AST/ALT <2.5 X institutional upper limit of normal Adequate hematological lab values including Absolute Neutrophil count (ANC) ≥ 1.0 x 109/L Any other cancer from which the patient has been disease-free for less than 3 years (except treated and cured basal-cell or squamous-cell skin cancer, superficial bladder cancer, or treated carcinoma in situ of the cervix, breast, or bladder and treated localized prostate cancer with undetectable PSA for 2 years) Symptomatic untreated metastases in the central nervous system Subject that is pregnant or lactating Pre-existing uncontrolled hypertension defined as >140/90 mm Hg with medication Known HIV or acquired immunodeficiency syndrome-related disease Prolongation of QTc interval (>480 ms). QTc interval per Bazett formula Uncontrolled diabetes [fasting glucose >1.5 × upper limit of normal (ULN)] (it will be acceptable if labs were done non-fasting and met the fasting requirement (meaning glucose < 1.5 ULN) Fasting total cholesterol >300 mg/dL and fasting triglyceride levels >2.5 × ULN (it will be acceptable if labs were done non-fasting and met the fasting requirement (meaning total cholesterol <300 mg/dL and triglyceride levels < 2.5 × ULN Proteinuria (defined by >2gm/ 24 hours urine protein if urinalysis is >2+) Significant cardiovascular impairment: History of (a) congestive heart failure greater than New York Heart association (NYHA) Class II, (b) unstable angina, (c) myocardial infarction (d) stroke, or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Gout CKD Stage 1-4 SUA Level (>8 mg/dL; 480 µmol/L) outpatient adults withgout and hyperurecemia (SUA level above 8 mg/dL (480 µmol/L) outpatient adults with CKD 1-4 stages and hyperurecemia (SUA level above 8 mg/dL (480 µmol/L) CKD 5 stage heart failure III-IV NYHA stroke peripheral arterial disease obesity with BMI above 30 kg/m2 hypertension 3 grade insulin-dependent DM any kind of cancer inpatient intensive unit patients | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-50.0, Persistent Post-Concussive Syndrome Man or woman aged 18-50 years. 2. Reports at least one PCS symptom that is mild in severity. 3. It has been two weeks since date of injury Has been previously diagnosed with a psychological/neurological disorder 2. Has been previously diagnosed with a substance abuse disorder/impairment, 3. Is currently seeking therapy/counseling 4. Does not have valid driver's license and 12 months of driving experience | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma ≥ 18 years of age. 2. Diagnosis of CLL or SLL. 3. Received at least one prior anti-cancer therapy for CLL or SLL. 4. Previous exposure to BTKi and meet at least one of the below: 1. Progressive disease (PD) while receiving or within 6 months after completing BTKi therapy. 2. Discontinued a BTKi therapy due to BTKi treatment related intolerance. 5. Measurable disease with a lymph node or tumor mass > 1.5 cm in at least one dimension. 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 7. Resolution of toxicities due to prior BTKi therapy to acceptable level. 8. Willingness of male and female patients to use medically acceptable methods of birth control. 9. Willing and able to participate in all required study evaluations and procedures Richter's transformation or prolymphocytic leukemia 2. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia 3. Received prior transplant 4. Experienced PD or serious adverse events on a prior phosphoinositide-3-kinase (PI3K) inhibitor 5. Known central nervous system involvement by CLL/SLL | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Parkinson's Disease Diagnostic of Parkinson's disease by a neurologist Native French speaker Affiliated to social security Unmodified PD treatment for at least 2 weeks before the Over 18 years-old Accepting the study after reading the information note and signing the consentment form Diagnostic of bipolar disorder or schizophrenia Abuse and dependence on psychoactive substances according to the DSM V Disabling sensory disorders Mental retardation or cognitive deterioration (e.g. dementia), with the incapacity to answer to the questionnaires Patients under guardianship or curatorship | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Cellular Diagnosis, Chronic Lymphocytic Leukemia All patients are newly diagnosed as CLL patients with associated malignancies | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Experimental Diagnosed as Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) according to "2016 WHO classification of tumors of haematopoietic and lymphoid tissues"; 2. Patients must have received systemic treatment (including chemotherapy or Hematopoietic stem cell transplantation), but did not achieve remission or had relapse after remission; 3. At least one measurable lesion; 4. Age 18-75 years, male or female; 5. ECOG performance status 0-1; 6. Without bone marrow involvement. Blood routine test: absolute neutrophil count ≥1.5 × 109/L, platelet ≥80 × 109/L, Hb ≥ 90g/L;. 7. Life expectancy no less than 3 months; 8. Not received chemotherapy, targeted medicine or stem cell transplantation 3 weeks before enrollment; 9. Patients have signed the Informed Consent Form Women during pregnancy or lactation, or fertile women unwilling to take contraceptive measures. 2. QTc elongation with clinical significance ( male˃ 450ms, female˃ 470ms), ventricular tachycardia, atrial fibrillation, cardiac conducting blockage, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease that requires treatment; 3. pericardial effusion ≥10mm sum of echo-free spaces by echocardiography; 4. Patients have undergone organ transplantation; 5. Patients received symptomatic treatment for bone marrow toxicity within 7 days prior to enrollment. 6. Patients with active hemorrhage. 7. Patients with or with history of thrombosis, embolism, cerebral hemorrhage, or cerebral infarction. 8. Patients with active infection, or with continuous fever within 14 days prior to enrollment. 9. Had major organ surgery within 6 weeks prior to enrollment. 10. Impaired liver function ( Total bilirubin ˃ 1.5 times of normal maximum, ALT/AST˃ 2.5 times of normal maximum, for patients with infiltrative liver disease ALT/AST ˃ 5 times of normal maximum), impaired renal function (serum creatinin˃ 1.5 times of normal maximum). 11. Patients with mental disorders or those do not have the ability to consent. 12. Patients with drug abuse, long term alcoholism that may impact the results of the trial. 13. Patients who have central nervous system involvements; 14. Non-appropriate patients for the trial according to the judgment of the investigators | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Acute Myeloid Leukemia Signed written informed consent according to ICH/EU/GCP and national local laws (if applicable) Patients aged ≥18 years affected by AML according to the FAB previously enrolled in Studies for AML treatment. AML patients with CNS involvement defined by the confirmation of leukemic blast cells in the centrifuged cerebrospinal fluid (CSF) with the presence of more than five WBCs in the CSF or the detection of a CNS granulocytic sarcoma using computed tomography or magnetic resonance imaging Patients with acute promyelocytic leukemia (FAB M3 subtype), antecedent haematological diseases or therapy-related AML | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, B Cell Lymphocytic Leukemia B Cell Non-Hodgkin's Lymphoma New diagnosis of CD20 expressing B-NHL or CLL o Up to 1/3rd of enrolled patients may have CLL. Enrollment of patients with CLL will be halted if this criterion is reached Will receive an anti-CD20 monoclonal antibody treatment (including rituximab, obinatuzumab) during the induction phase of treatment Has not previously received cytotoxic chemotherapy medications Able to provide informed consent Comorbidities or frailty that would limit estimated survival to <1 year Will not receive active anti-CD20 containing remission induction therapy | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Aortopathies Thoracic Aortic Aneurysm Aortic Valve Disease Thoracic Aortic Disease Thoracic Aortic Dissection Thoracic Aortic Rupture Ascending Aortic Disease Descending Aortic Disease Ascending Aortic Aneurysm Descending Aortic Aneurysm Marfan Syndrome Loeys-Dietz Syndrome Ehlers-Danlos Syndrome Shprintzen-Goldberg Syndrome Turner Syndrome PHACE Syndrome Autosomal Recessive Cutis Laxa Congenital Contractural Arachnodactyly Arterial Tortuosity Syndrome Open to external enrollment Subjects with a genetic diagnosis of Marfan Syndrome (MDS), Loeys-Dietz Syndrome (LDS), or Vascular Ehlers-Danlos Syndrome (EDS); (Positive genetic testing or a previous cardiac study required to be eligible) Family members of eligible subjects (Only family members of subjects with syndromic diagnoses are eligible for external enrollment at this time) Closed to external enrollment Subjects with aortic disease including TAA* or dissection, aortic tortuosity, or aortic hypoplasia/stenosis (based on any cardiac imaging modality including echocardiography, CT, MRI, or angiography) Subjects with aortic valve disease (bicuspid, unicuspid, or tricuspid disease) Control subjects having tissue removed during a surgical procedure (e.g. coronary artery bypass graft surgery (CABG), cardiac transplant, etc.) • Inability or unwillingness to provide consent (assent when indicated) | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Autoimmune Cytopenia Associated With Chronic Lymphocytic Leukemia Patient with CLL Active autoimmune cytopenia Initiation of a treatment with ibrutinib or idelalisib for autoimmune cytopenia Other lymphoid hemopathy B Absence of documentation of the autoimmunity of cytopenia | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Clinical diagnosis of Chronic Lymphocytic Leukemia and has a toxic heavy metal load Toxic heavy metal load Pregnant Pacemaker implants Organ transplant recipients Psychotic episodes or epileptic seizures | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Have high risk CLL Have documented previously untreated CLL according to IWCLL Willing and able to provide written informed consent Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Demonstrate adequate organ function Able to take oral medication and willing to adhere to the medication regimen Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment Meets IWCLL to start therapy Has had any treatment for CLL including any investigational agent, chemotherapy, mAb, anti-PD-1, anti-PDL-1, or anti-CTLA-4 Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia) Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment Major surgery or a wound that has not fully healed within 4 weeks of first dose Additional may apply | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 6.0-999.0, Gaucher Disease, Type III Gaucher disease patients diagnosed by low B-glucocerebrosidase deficiency and GBA mutation The participant is at least 6 years old at time of enrollment Under stable Cerezyme dosage for at least for 3 months Presence of lymphadenopathy Patient (and/or their parent/legal guardian) is willing to participate and able to provide signed informed consent The participant is CYP2D6 ultra-rapid metabolizer The participant had received substrate reduction therapy for Gaucher disease within 3 months of enrollment The participant had any clinically significant disease other than GD, including cardiovascular (especially arrhythmia), renal, liver, pulmonary, endocrinopathy, hypokalemia, or hypomagnesemia that may confound the study result The participant is pregnant or lactating The participant is known to be allergy to Cerdelga The participant use drugs that will strongly inhibit CYP2D6 or CYP3A activity | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Von Willebrand Disease Historically lowest VWF:Ag and/or VWF:RCo and/or VWF:CB ≤ 0.30 IU/mL and/or FVIII:C ≤ 0.40 IU/mL Treatment at a Hemophilia treatment center in the Netherlands All types of VWD All ages Other known bleeding disorders present | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Richter Syndrome Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma requiring therapy, as per IW-CLL 2008 OR Biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's Syndrome Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy If Richter's Syndrome, this criterion is not applicable Age greater to or equal to 18 years ECOG performance status ≤2 (Karnofsky ≥60%) Patients must meet the following hematologic at screening, unless they have significant bone marrow involvement of CLL confirmed on biopsy Absolute neutrophil count ≥500 cells/mm3 (0.5 x 109/L). Growth factor is allowed in order to achieve this Platelet count ≥25,000 cells/mm3 (25 x 109/L) independent of transfusion within 7 days of screening Adequate hepatic function defined as: --Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN), bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin Adequate renal function as defined as: --Serum creatinine ≤1.5 times the upper limit of normal or creatinine clearance ≥ 50 mL/min using a 24-hour urine collection Previous treatment with venetoclax or duvelisib Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, surgery within 2 weeks of Cycle 1/Day 1 with the following exceptions For patients on targeted therapies, a washout of least five half lives is required Patients who experience clinical deterioration may start therapy after a shorter washout period with prior approval by the PI Corticosteroid therapy (prednisone or equivalent <20 mg daily) is allowed Confirmed central nervous system involvement Allogeneic hematologic stem cell transplant within 6 months of starting study treatment or active graft vs. host disease (GVHD) requiring treatment or prophylaxis History of active malignancy requiring therapy with the exception of hormonal therapy Any active systemic infection requiring IV antibiotics or uncontrolled, active infections Known history of human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Decompensated Cirrhosis chronic active HCV proved by the positivity of HCV RNA, elevated transaminases CTP score was >9, MELD score was <29 Decompensated cirrhosis with frequent hepatic encephalopathy (HE) or difficult to treat ascites exposure to previous antiviral therapy hepatocellular carcinoma other causes of liver diseases or mixed causes (excessive alcohol consumption, autoimmune liver disease) previous liver transplantation | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-100.0, Diffuse Large B-cell Lymphoma(DLBCL) Mantle Cell Lymphoma (MCL) Follicular Lymphoma (FL) Subject has provided informed consent prior to initiation of any study-specific activities/procedures Age ≥ 18 at the time of informed consent Biopsy proven B-NHL including DLBCL, which also includes DLBCL that represents transformation of indolent NHL (including follicular, marginal zone, and lymphoplasmacytic lymphoma excluding chronic lymphocytic leukemia or Hodgkin Lymphoma) and DLBCL with alterations of MYC and BCL2 and/or BCL6 also described as double-hit and triple-hit lymphomas MCL Presentations of these histologies with substantial occurrence of malignant cells into the bloodstream (lymphocyte count ≥ 7 x 10^9/L) including all leukemic presentations are excluded. The following histologies are not eligible: Lymphoblastic lymphoma Burkitt lymphoma Any histologies not specifically mentioned must be discussed with the Medical Monitor Subjects with transformation of indolent lymphoma must have received therapy after a diagnosis of transformation that is appropriate for aggressive histology Subjects who received prior CD19-targeting treatment are allowed (CAR-T cell therapy is excluded). A biopsy following CD19-targeting treatment is required unless no lesions are accessible or the risk of the biopsy is deemed too high by the investigator For Part 2 (Expansion in patients with DLBCL): only biopsy proven DLBCL (biopsy proven at least at primary diagnosis), including DLBCL that represents transformation of indolent NHL (including follicular, marginal zone, and lymphoplasmacytic lymphoma excluding chronic lymphocytic leukemia or Hodgkin Lymphoma) are eligible. Other histologies are not eligible Presentations of these histologies with substantial occurrence of malignant cells into the bloodstream (lymphocyte count ≥ 7 x 10^9/L) including all leukemic presentations are excluded Subjects with transformation of indolent lymphoma must have received therapy after a diagnosis of transformation that is appropriate for aggressive histology as described in criterial Subjects who received prior CD19-targeting treatment are allowed (CAR-T cell therapy is excluded) A biopsy following CD19-targeting treatment is required unless no lesions are accessible or the risk of the biopsy is deemed too high by the investigator Treatment within 30 days prior to enrollment with another investigational device or drug (interventional clinical study / studies). Other investigational procedures while participating in this study are excluded (observational studies are permitted) Prior anti-cancer therapy as specified below At least 6 weeks must have elapsed since any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc) before the first dose of AMG 562 Other targeted anti-cancer therapy (chemotherapy, molecular targeted therapy, steroids) within 14 days or 5 half lives (which ever is longer) prior to first dose of AMG 562. Patients requiring continued treatment due to aggressive disease may only be included if there is agreement by both the investigator and the Amgen Medical Monitor Radiation therapy completed within 28 days prior to first dose of AMG 562 Autologous HSCT within six weeks prior to start of AMG 562 treatment At least 4 weeks must have elapsed since any prior treatment with antibody therapy (exception immune checkpoint inhibitors) before the first dose of AMG 562 Prior CD19-directed CAR-T cell therapies Prior allogeneic HSCT For Part 2 (Expansion in patients with DLBCL): fluorodeoxyglucose non-avid patients | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia CLL SLL Small Lymphocytic Lymphoma Be ≥18 years old 2. Have an established, pathologically confirmed diagnoses of CLL/ Small Lymphocytic Lymphoma (SLL) requiring therapy according to the 2018 IWCLL guidelines 3. Have received at least one prior therapy for CLL/SLL and can be classified in one of two patient groups Group 1 (TP-0903 monotherapy): Patients with CLL/SLL who are intolerant to, or have progressed on B-cell receptor antagonists and/or BCL-2 antagonists or other investigational treatments for CLL/SLL Group 2 (TP-0903 and ibrutinib combination therapy): Patients with CLL/SLL who have progressed on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 5. Have adequate hematologic function Absolute neutrophil count (ANC) ≥500/µL Platelet count ≥30,000/µL Hemoglobin ≥8 g/dL in the absence of transfusions within the previous 2 weeks 6. Have adequate organ function Creatinine clearance ≥30 mL/min Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤2.5 × upper limit of normal (ULN) Have a total bilirubin level ≤1.5 × ULN (unless secondary to Gilbert syndrome, hemolysis, or leukemia) 7. Have acceptable coagulation status: • Activated partial thromboplastin (aPTT) and prothrombin time (PT) ≤1.5 × ULN 8. Have a negative pregnancy test (if female of childbearing potential) 9. Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception (hormonal or barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation and for at least 30 days after the last study drug dose. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. 10. Have read and signed the Institutional Review Board (IRB) approved informed consent form (ICF) prior to any study related procedure. (In the event that the patient is rescreened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.) 11. Are able to comply with the requirements of the entire study Have undergone prior autologous or allogeneic stem cell transplant within ≤3 months, have not recovered from transplant associated toxicities, or requires graft versus host immunosuppressive therapy 2. Have known central nervous system (CNS) involvement 3. Have Richter's transformation of CLL 4. Have received any monoclonal antibody therapy directed at treatment of the patient's malignancy within 2 weeks prior to anticipated first dose 5. Have received any anticancer therapy including chemotherapy, radiotherapy, or an investigational anticancer drug within less than 5 half lives of the last dose of that treatment • This criterion is not applicable to patients requiring continuation on ibrutinib. (Note: Certain patients with a rapidly rising white blood cell count while on ibrutinib may need to remain on this drug for medical reasons. These patients will need to be approved by the Medical Monitor and treated in accordance with the protocol.) 6. Have received >20 mg/day of prednisone and 0.1 mg/day of mineralocorticoids within 7 days prior to anticipated first dose 7. Have a corrected QT interval of >450 msec (males) and >470 msec (females) using Fridericia's correction formula 8. Have a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, or cardiovascular disease or any other medical condition that, in the opinion of the Investigator, would adversely affect his/her participation in the study 9. Are pregnant and/or nursing, or refuse to use appropriate contraceptives during the course of the study and for at least 30 days after the last dose of study drug 10. History of another malignancy in the last 5 years except for the following adequately treated Local basal cell or squamous cell carcinoma of the skin Carcinoma in situ of the cervix or breast Papillary, noninvasive bladder cancer Early stage prostate cancer for which observation is clinically indicated Other Stage 1 or 2 cancers currently in complete remission Any other cancer that has been in complete remission for 2 years or surgically cured. Medical Monitor may be contacted for additional determination of acceptable prior cancer history 11. Have known gastrointestinal disorders (eg, malabsorption syndrome), complications (eg, dysphagia), or surgery that could make consumption or absorption of oral medications problematic 12. Have an uncontrolled systemic infection (viral, bacterial, or fungal) or fever and neutropenia within 7 days prior to anticipated first dose 13. Have active and uncontrolled autoimmune cytopenias for 2 or more weeks including autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) 14. Have received prior therapy with an AXL inhibitor 15. Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation 16. Are unwilling or unable to comply with procedures required in this protocol 17. Have a history of severe adverse reaction (eg. hypersensitivity reaction, anaphylaxis) to sulfonamides | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia (CLL) Subjects must have CLL or SLL In cohort 2, subjects must have TP53-aberrant disease defined as Del(17p) detected on karyotype and/or FISH; OR TP53 mutation Participants must have measurable disease (lymphocytosis > 5,000 / µl, or palpable or CT measurable lymphadenopathy ≥ 1.5 cm, or bone marrow involvement ≥30%) Subjects must not have received any prior systemic therapy for CLL or SLL due to meeting IWCLL 2018 guidelines and must currently have an indication for treatment as defined by the IWCLL 2018 guidelines Massive or progressive or symptomatic splenomegaly; OR Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR Significant fatigue (i.e. ECOG PS 2 or worse; cannot work or unable to perform usual activities); OR Fever ≥ 100.5°F for 2 or more weeks without evidence of infection; OR Participants who have a history of other malignancies except Malignancy treated with curative intent and with no known active disease present and felt to be at low risk for recurrence by treating physician. Current adjuvant hormonal therapy for disease treated with curative intent is permissible Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Low-risk prostate cancer on active surveillance Participants who are receiving any other investigational agents History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to obinutuzumab, venetoclax, or acalabrutinib. Patients with reactions to other CD20 monoclonal antibodies (e.g. rituximab, ofatumumab) are not excluded Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), and herpes zoster (VZV) at start of treatment Known or suspected Richter's transformation or known CNS involvement Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., within 28 days of the first dose of study drug or chronic administration of >20 mg/day of prednisone within 7 days of the first dose) | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Cirrhosis Hepatic Encephalopathy Minimal Hepatic Encephalopathy Covert Hepatic Encephalopathy Age >18 years 2. Cirrhosis defined by any one of the following 1. Cirrhosis on liver biopsy or transient wave elastography 2. Nodular liver on imaging 3. Endoscopic or radiological evidence of varices in a patient with chronic liver disease 4. Platelet count <150,000/mm3 and AST/ALT ratio >1 in a patient with chronic liver disease 5. Patients with frank decompensation (ascites, HE, variceal bleeding, hepato-pulmonary syndrome) 3. Prior HE controlled on standard of care therapy defined as lactulose or rifaximin for at least 2 months prior to enrollment. 4. Serum albumin <4 gm/dl 5. Cognitive impairment on any of the three testing strategies for HE including Psychometric hepatic encephalopathy score (PHES), Stroop test and Critical Flicker Frequency 1. PHES aggregate score <-4SD based on norms published in Allampati et al located at the website www.encephalapp.com 2. Stroop OffTime+OnTime values greater than norms published in Allampati et al located at the website www.encephalapp.com 3. Critical Flicker Frequency value <39 Hz Unclear diagnosis of cirrhosis (does not meet the outlined above) 2. No prior overt HEepisodes 3. HE uncontrolled on standard of care defined as a mini-mental status exam<25 4. On regular IV albumin infusions due to scheduled paracentesis within the last 3 months 5. Recent alcohol abuse (within 3 months) 6. Unable to give consent 7. Current or recent invasive bacterial or fungal infections (<1 month) 8. Allergic reactions to IV albumin 9. Current or recent congestive heart failure (Systolic ejection fraction <25%) within the last year 10. Pregnancy (positive urine pregnancy test at screening) 11. In the opinion of the PI, those who are unlikely to survive 6 weeks or be able to adhere to the trial activities | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-99.0, Chronic Lymphocytic Leukemia Age ≥ 18 years of age Diagnosed with CLL To be considered CLL, the subject must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells Histologic and immunophenotypic analysis should demonstrate small to moderate size lymphocytes with flow cytometry demonstrating a certain population of lymphocytes No prior therapy for their disease. Topical or inhaled corticosteroids are permitted for other medical conditions, ie asthma or dermatologic reasons Eastern Oncology Cooperative Group (ECOG) performance score of ≤ 2 Subjects with autoimmune hemolytic anemia or autoimmune thrombocytopenia will be eligible for treatment on this protocol regardless of disease stage upon discussion with the principal investigator An absolute neutrophil count > 1.0 109/L; hemoglobin > 8 g/dL; or a platelet count > 50 x 109/L (unless due to bone marrow failure) Adequate hepatic function activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5x the upper limit of reference ranges Subjects who have been previously treated for CLL or small lymphocytic lymphoma (SLL), except with corticosteroids for symptom relief Treatment with any of the following within 7 days prior to the first dose of study drug Steroid therapy for anti-neoplastic intent moderate or strong cytochrome P450 3A (CYP3A) inhibitors moderate or strong CYP3A inducers Subject has known allergy to both xanthine oxidase inhibitors and/or rasburicase Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study Subject has evidence of other clinically significant uncontrolled condition(s) including, but not limited to: 1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal) 2. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate Subject is known to be positive for HIV. (HIV testing is not required.) New York Heart Association (NYHA) class II-IV heart failure or arrhythmia requiring treatment | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Richter Syndrome Diagnosis of a Diffuse Large B-Cell Lymphoma arising in the context of a Chronic Lymphocytic Leukemia (group 1) or diagnosis of a primitive Diffuse Large B-Cell Lymphoma (group 2), or diagnosis of a Diffuse Large B-Cell Lymphoma arising in a context of small cells lymphoma, excluding CLL (group 3), or benefit from a diagnostic lymph node biopsy that did not reveal any tumor involvment (primitive or metastatic) (group 4) Patients must benefit from a lymph node biopsy at diagnosis Patients must be followed by a FILO (French Innovative Leukemia Organization) member Histology of Diffuse Large B-Cell Lymphoma or Hodgkin histology Suitable clinical data available Samples must meet the following requirement :RIN (RNA Integrity Number) > 5 et DIN (DNA Integrity Number) > 6.5 • Samples that do not meet the (insufficient clinical data, analysis impossible due to insufficient sample quality) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, FLT3-ITD Mutation AML Patients with AML carrying Flt3 mutation; AND Patients with persistent leukemia despite at least two prior chemotherapy regimens Patients who are considered not fit for any form of leukemia treatment by the attending hematologists | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Comprehensive Education Patients over the age of 18 years undergoing routine gastroscopy 2. Informed consent Serious coronary heart disease and myocardial injury with serious heart failure 2. Stenosis of the esophagus or cardia obstruction 3. Acute pharyngitis and tonsillitis 4. Acute upper gastrointestinal bleeding 5. Hemodynamically unstable 6. allergy to topical lidocaine 7. Patients did not cooperate or spirit was not normal 8. Pregnancy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Haemophilia B Have a diagnosis of haemophilia B and been treated previously with factor IX Product Have started Alprolix treatment prior to enrolment visit, or at enrolment prescribed treatment with Alprolix, regardless of participation in the study Signed and dated informed consent provided by the patient, or the patient's legally acceptable representative for patients under the legal age, before any study-related activities are undertaken. Assent should be obtained from paediatric patients according to local regulations Participation in an investigational medicinal product trial at enrolment visit | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-65.0, HSV Herpes Labialis Age ≥18 and <65 2. Positive test for IgG against herpes simplex virus type 1 (HSV-1). 3. Groups A and B only: Clinical diagnosis of herpes labialis, which may be made at the screening visit based on the patient's self-reported history of symptoms. An active herpes labialis outbreak at the time of entry into the clinical trial will neither be required nor will be an 4. Group A only: Self report having six or more episodes of herpes labialis in the past 12 months. Subjects will NOT be told that six-or-more episodes in the previous 12 months is the entry criterion. Subjects will be asked "How many separate episodes of cold sores have you had in the previous 12 months?" They will be included if they give an answer of six or more and excluded from Group A if they give an answer of five or fewer. 5. Group A only: At least half of the subject's episodes of the previous 12 months should be vesicular in nature and at least half preceded by prodromal symptoms. 6. Group B only: Self report having exactly 1 or 2 episodes of herpes labialis in the past 12 months. Subjects will NOT be told that one or two episodes in the previous 12 months is the entry criterion. Subjects will be asked "How many separate episodes of cold sores have you had in the previous 12 months?" They will be included if they give an answer of one or two and excluded from Group B if they give a different answer. 7. Group C only: Self report having zero episodes of herpes labialis in the past 12 months. Subjects will NOT be told that zero episodes in the previous 12 months is the entry criterion. Subjects will be asked "How many separate episodes of cold sores have you had in the previous 12 months?" They will be included if they give an answer of zero and excluded from Group C if they give an answer of one or more Pregnant or lactating females. 2. Current or recurrent non-herpetic infection or any underlying condition that may predispose to infection or anyone who has been admitted to the hospital due to bacteremia, pneumonia or any other serious infection in the last 12 months. 3. Therapy with glucocorticoid or immunosuppressants at time of recruitment or within past 4 weeks prior to the screening visit (including inhaled corticosteroids for asthma), except for topical steroids in sites other than face. 4. History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers). 5. History of organ transplantation. 6. HIV-positive status determined by history at screening or known history of any other immunosuppressive disease. 7. Severe co-morbidities (diabetes mellitus requiring insulin, CHF (NYHA class II or worse) MI, CVA or TIA within 3 months of screening visit, unstable angina pectoris, oxygen-dependent severe pulmonary disease 8. Known hypersensitivity to Dimethyl sulfoxide (DMSO). 9. Any condition judged by the investigator to cause this clinical trial to be detrimental to the patient. 10. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit. 11. Previous exposure to SADBE (squaric acid or squaric acid dibutyl ester). 12. Subject has an abnormal skin condition (e.g., acne, eczema, rosacea, psoriasis, albinism, or chronic vesiculo-bullous disorder) that occurs in the area ordinarily affected by herpes labialis. 13. Subject has had a vaccine for either HSV-1 or HSV-2. 14. Group A only: People that have had treatment with anti viral therapy within 2 weeks before sensitization dose of SADBE. 15. Groups B and C only: People that have had treatment with anti-viral therapy any time in the past 12 months | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.167-0.5, Severe Acute Malnutrition Group 1 (SAM) Infants between 2 and <6 months old with SAM as defined by weight-for-length < -3 Z and/ or bilateral pedal edema either sex caregiver willing to provide consent for enrolment of the infant caregiver willing to stay in the Nutritional Rehabilitation Unit for about 15 days residence within 15 km from icddr,b Group 2 (non-malnourished) Non-malnourished infants (WLZ ≥ -1) <6 months old who are hospitalized for treatment with antibiotics for infection (infants who come with a history of antibiotic intake for 3 days or more will be eligible; the last dose of such an antibiotic will have to be taken within last 24hours, the antibiotic intake should be documented by the verification of a prescription, the bottle of antibiotic or asking the caregiver about the name of antibiotic or its price and how it is reconstituted) infant receiving at least 50% of nutritional intake from breast milk at the time of hospitalization either sex residence within 15 km from icddr,b Septic shock or very severe pneumonia requiring assisted ventilation acute kidney injury on admission congenital defects interfering with feeding such as cleft palate chromosomal anomalies jaundice tuberculosis presence of bilateral pedal edema ongoing maternal antibiotic usage for breastfeeding infants Group 1 (SAM) additional Infants receiving ≥75% of nutrition from breast milk Group 2 (non-malnourished) additional Infants receiving <50% of nutrition from breast milk | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Relapsed/Refractory Large B-cell Lymphoma Key Histologically proven large B-cell lymphoma including the following types Diffuse large B cell lymphoma (DLBCL) not otherwise specified (ABC/GCB) High grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6 rearrangement DLBCL arising from follicular lymphoma T cell/histiocyte rich large B-cell lymphoma DLBCL associated with chronic inflammation Primary cutaneous DLBCL, leg type Epstein-Barr virus (EBV) + DLBCL Relapsed or chemotherapy-refractory disease, defined as one or more of the following Histologically proven primary mediastinal B-cell lymphoma (PMBCL) History of Richter's transformation of chronic lymphocytic lymphoma (CLL) Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy History of severe, immediate hypersensitivity reaction attributed to aminoglycosides History of HIV infection or acute or chronic active hepatitis B or C infection. Individuals with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or a history of CNS lymphoma History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement Individuals with cardiac atrial or cardiac ventricular lymphoma involvement History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment Requirement for urgent therapy due to tumor mass effects (eg, blood vessel compression, bowel obstruction, or transmural gastric involvement | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Mucopolysaccharidosis II Patients who will have completed clinical trial JR-141-BR21 Capable of providing written consent by himself, unless the patient is under the age of 18 years at the time of informed consent process, or it is not possible to obtain consent from the patient himself due to his intellectual disabilities associated with MPS II In the case of a patient who is under the age of 18 years or from whom it is not possible to obtain consent due to his intellectual disabilities associated with MSP II, he may be included if written consent can be provided by legal representative; however written consent should be obtained from the patient himself too, wherever possible Refusal to sign the informed consent form Unable to perform the study procedures, except for neurocognitive testing Previous engrafted BMT/HSCT Judged by the investigator or subinvestigator as being unable to undergo lumbar puncture, including those who have difficulties in taking a position for lumber puncture due to joint contracture or those who are likely to experience difficulty breathing during the lumbar puncture process Judged by the investigator or subinvestigator to be ineligible to participate in the study due to a history of a serious drug allergy or sensitivity Otherwise judged by the investigator or subinvestigator to be ineligible to participate in the study out of consideration for the subject safety | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-70.0, Cirrhosis for EHM+ subjects Age between 18 and 70 (inclusive) Cirrhosis Minimal hepatic encephalopathy Expression of non opposition for EHM subjects Age between 18 and 70 (inclusive) Cirrhosis No hepatic encephalopathy (minimal or clinical) Paired with EHM+ subjects about age, gender, MELD score and cirrhosis etiology for all subjects Age older than 70 MMS score < 24 Clinical hepatic encephalopathy Cirrhosis etiology different from alcoholic, viral or metabolic one Intake of psychotropic drugs within 48h Alcohol intake > 30 g/j Heart, renal or respiratory failure Evolutive neurological diseases History of neurological diseases causing consequences | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 8.0-65.0, CTLA4 Haplonisufficiency Chronic Cytopernia Individuals must meet all of the following to be eligible for study participation: 1. Age 8-65 years. 2. Documented CTLA4 mutation (requires documentation of confirmed mutation via Sanger sequencing at a laboratory approved by the Clinical Laboratory Improvement Amendments [CLIA]). 3. At least one of the following established hematologic abnormalities during the past 6 months (including results from outside CLIA-certified laboratories) prior to screening ANC < 750 cells/microL Platelet count < 75,000 cells/microL Hemoglobin < 7.5 g/dL. 4. The above mentioned hematologic abnormalities should require active treatment with steroids, immunomodulatory agents (e.g., mycophenolate mofetil, cyclosporine, tacrolimus, mercaptopurine, methotrexate, sirolimus, high dose intravenous immunoglobulin [IVIG]), and/or other agents (e.g., TPO agonists) for at least 60 days prior to screening. 5. The dose of any concomitant medication(s) aimed at treating cytopenia should be stable in the 60 days prior to screening. Stable is defined as No new concomitant medications for cytopenia were initiated No dose increase of the medication was required. 6. Did not receive blood product transfusions within 30 days prior to screening. 7. Did not receive abatacept within 60 days prior to screening. 8. Did not receive rituximab within 3060 days of screening. 9. Did not receive alemtuzumab at any time. 10. Has access to healthcare provider at home. 11. Able to provide informed consent. 12. Willing to allow storage of biological specimens for future use in medical research. 13. Females of childbearing potential must agree to use appropriate birth control methods when engaging in sexual activities that can result in pregnancy, beginning Day -30 through 30 days after the last dose of study agent. Appropriate methods should 2 forms of contraception, one from each of the following categories Hormonal contraception or placement of an intrauterine device or intrauterine system Barrier method: Condom or occlusive cap (diaphragm or cervical/vault cap) with a spermicide Patients meeting any of the following are not eligible for this study: 1. History of hypersensitivity to abatacept. 2. Any live vaccines (including attenuated live vaccines) within 6 weeks of screening. 3. History of acquired immunodeficiency diseases, including a positive HIV polymerase chain reaction (PCR) test result. 4. Untreated chronic hepatitis B (positive PCR) or hepatitis C (positive PCR) infection. Patients with chronic hepatitis must be on medical treatment for at least 3 months before screening and have evidence of decreased viral loads after starting treatment. 5. EBV viral load > 4log on 2 or more laboratory checks greater than 1 month apart and within 6 months of screening. 6. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of evidence of local recurrence or metastases. 7. Current active infectious disease (bacterial or fungal) including evidence of tuberculosis (TB) infection as defined by a positive QuantiFERON TB-Gold test. Test results within the past 6 months will be accepted. If presence of latent TB is established, then treatment must be completed before the patient can be considered for enrollment. The patient may also be considered for enrollment after completing treatment of any other active bacterial or fungal infection. 8. Contraindication to PFT or CT scan. 9. Pregnancy or breastfeeding. 10. Any condition that, in the opinion of the investigator, contraindicates participation in this study | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Relapsed or Refractory Chronic Lymphocytic Leukemia CLL that is relapsed or refractory to BTK inhibitors and is on a stable dose of venetoclax ECOG 0-2 Adequate bone marrow function Adequate renal function Adequate liver function INR <=1.2 in patients not receiving chronic anticoagulation At least 4 weeks from prior cytotoxic chemotherapy At least 4 weeks from major surgery Agree to practice effective contraception Known CLL involvement in CNS that is symptomatic and active currently receiving radiotherapy, biological therapy, or any other investigational agents Uncontrolled intercurrent illness Pregnant or lactating Known to be HIV-positive Known active hepatitis B and/or hepatitis C infection | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Lymph Node Disease clinically enlarged lymph nodes previous medical treatment or radiotherapy previous biopsy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Arthroplasty, Replacement, Knee Preoperative Patient is undergoing a unilateral total knee arthroplasty procedure; and Patient is willing and able to give written informed consent for registry participation. Preoperative Patient has a known sensitivity or allergy to bovine and/or porcine substance(s); and Patient has religious or other objections to porcine, bovine, or human components. Intraoperative Patient has at least one Target Bleeding Site (TBS) with minimal, mild, or moderate bleeding for which conventional means for hemostasis are ineffective or impractical; and The surgeon elects to utilize Bellows per its approved Indication for Use | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 20.0-999.0, Biliary Tract Cancer Histologically confirmed BTC (cholangiocarcinoma or gall bladder (GB) cancer) , except ampulla of Vater cancer 2. In the event that the progression of the gemcitabine/cisplatin is experienced during or after discontinuation of the first line treatment for metastatic, locally advanced or relapsed (it may be considered as a first line treatment that recurrence within six months of completion of the adjuvant or neo-adjuvant chemotherapy using gemcitabine/cisplatin) 3. Patient (or legal representative) has completed an approved consent documents that he or she will participate in the test after receiving sufficient information about the clinical trial 4. East clinical oncology group (ECOG) performance status 0-1 5. One or more measurable lesions by v1.1. 6. Appropriate organ functions; A. Liver: bilirubin ≤ 3 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN (in cases of liver metastasis, AST or ALT ≤ 5 x ULN) B. Kidney: An estimate of creatine clearance rate according to the Cockcroft-Gault formula (or local institution's standard method) > 30 mili-liter (mL)/min C. Hemoglobin ≥ 9 g/dL (transfusion allowed), absolute neutrophil count (ANC) ≥ 1500/μL, platelet count ≥ 75,000/μL. 7. Expected life time over 3 months. 8. Over 19 years old. 9. In case of proper bile excretion function 10. Have the will and ability to comply with the clinical trial plan during the study period, including treatment and scheduled visits and examination. 11. For pre-menopausal women and for women less than one year after the onset of menopause, serum or urine pregnancy tests shall be confirmed negative during screening. 12. For men and fertile women, the use of effective contraceptive methods should be agreed (effective contraception should be used for at least 30 days prior to the initial administration of a investigational drug, the trial period, and at least 90 days after the discontinuation of the test participation) ≥ 2 of prior chemotherapy for progressive BTC (except for adjuvant/neo-adjuvant chemotherapy with resting of more than six months) 2. Symptomatic or untreated brain metastasis or spinal cord compression metastasis. 3. Previous treatment using Irinotecan or oxaliplatin 4. In case of major surgery within four weeks just before registration, excluding biopsy for diagnosis 5. In case of chemotherapy or radiation therapy was received within three weeks prior to the administration of a test medication 6. Grade 2 or higher peripheral neuropathy 7. Grade 2 or higher toxicities caused by a previous cancer treatment based on NCI-CTCAE v 4.03 other than hair loss 8. A person diagnosed with another malignant tumor within the last five years. Exceptions basal or squamous cell carcinoma of the skin or intraepithelial neoplasia (bladder, uterine cervical, colorectal, breast) 9. Pregnant or nursing woman 10. If there is a severe or uncontrolled systemic disease, active infection, active bleeding tendency or organ transplantation history (including allo-hematopoietic stem cell transplantation) 11. The following virus infection A. Known positive history for human immunodeficiency virus (Human Immunodeficiency virus, HIV) test or known acquired immunodeficiency syndrome (AIDS) B. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive Hepatitis B surface -Ag (+) or HCV RNA (+) if anti-HCV Ab screening test is positive) 12. If there is a known alcohol or drug abuse 13. In cases of clinically significant (i.e., active) cardiovascular disease: cerebral hemorrhage/brain infarction, myocardial infarction (pre-registration < 6 months), unstable angina, congestive heart failure (NYHA classification ≥2) or arrhythmia needed drug therapy. 14. In case of a mental state in which it is impossible to understand and provide the consent | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-78.0, Nursing Care Patient Education Patients hospitalised in preparation to receive LDH surgery and who volunteered to participate Older than 18 years Could read and write in Turkish Scored between 1 and 3 in the classification systems of the American Society of Anesthesiologists were preparing for their first LDH surgical operation Could use CD-based educational materials Patients hospitalised in preparation to receive LDH surgery and who unvolunteered to participate All potential participants who had previously undergone LDH surgery Could not use CD-based educational materials or had mental disorders liable to prevent communication | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Chronic Hepatitis B HBsAg positive, HBeAg negative, antibody to HBeAg-positive; 2. Stable administration of anti-HBV neucleos(t)ides analogue mono therapy for at least more than one and a half year; 3. Demonstration of undetectable HBV DNA on three occasions, each at least 6 months apart, which is consistent with the APASL stopping rule; 4. Patients read, understand the consent form, and signed the study consent Patient with other liver diseases; 2. Patient with concurrent hepatitis viruses or HIV infection; 3. Patients are reluctant to stop their anti-HBV treatment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 21.0-75.0, Cirrhosis Hepatic Encephalopathy Cirrhosis diagnosed by either of the following in a patient with chronic liver disease Liver Biopsy Radiologic evidence of varices, cirrhosis or portal hypertension Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1 Endoscopic evidence of varices or portal gastropathy Fibroscan values suggestive of cirrhosis On treatment for hepatic encephalopathy (patient can be on lactulose and rifaximin) Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting) Women of child bearing potential must agree to use effective contraception for the duration of the study and for 10 days prior and 30 days after the study Negative pregnancy test in women of childbearing age MELD score >22 WBC count <1000 cells/mm3 Platelet count<25,000/mm3 TIPS in place for less than a month Currently on antibiotics apart from rifaximin Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed) Hospitalization for any non-elective cause within the last 1 month Patients who are aged >75 years Patients who are pregnant or nursing (will be checked using a urine pregnancy test) Patients who are incarcerated | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-13.0, Hemophilia Hemophilia A Hemophilia B Hemophilia A With Inhibitor Hemophilia B With Inhibitor Haemophilia B Without Inhibitor Haemophilia A Without Inhibitor Haemophilia Congenital hemophilia A; FVIII </=5% or congenital hemophilia B; FIX </=5% Birth date on or after January 1, 2010 Care established at one of the participating HTCs Co-enrollment in the ATHNdataset; and Parent or authorized guardian can provide informed consent Patients who are referred to the HTC with no record of bleed and factor utilization data | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-45.0, Hepatitis E Immunisation Subject must provide written informed consent. 2. Subject must be able to comprehend and willing to comply with all study visits and procedures (up to 13 months from enrollment). 3. Subject must be a man or a non-pregnant woman* aged 18-45 years (inclusive). *Females of childbearing potential must have a negative serum human chorionic gonadotropin (beta-HCG) pregnancy test at screening and negative urine beta-HCG pregnancy test within 24 hours prior to (each) vaccination. 4. Subject must be in good general health as determined by medical history, vital signs*, body mass index (BMI)**, physical examination, and clinical judgment of the investigator. *Oral temp < 38.0 Degrees Celsius /100.4 Degrees Fahrenheit; pulse 51 to 100 bpm; systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mm Hg. **BMI > / = 18.5 and < 35 kg/m^2. 5. Subject's screening laboratory values*,** must be within site normal limits*** within 28 days of enrollment. *Screening labs will White blood cell (WBC) count; Hemoglobin (HgB); Platelets; Absolute neutrophil count (ANC); Absolute eosinophil count (AEC); Creatinine; Glucose (random, must be < 140); Alanine Aminotransferase (ALT); HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody. **Minor abnormalities are considered acceptable if not clinically significant (e.g., Mean Corpuscular Volume (MCV)). Repeating the screening tests once is permitted for out-of-range values provided there is an alternative explanation for the out-of-range value. The alternative explanation for the out-of-range value should be documented in the subject's source documents. ***Creatinine, glucose, and ALT values lower than the normal range may be acceptable if the PI or a designated licensed clinician determines that these laboratory findings are not clinically significant. The HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody must be non-reactive. 6. Subject's Hepatitis E Virus (HEV) specific Immunoglobulin G (IgG) and Immunoglobulin M (IgM) are negative by ELISA at screening. 7. Subject agrees to not to participate in another clinical trial during the study period. 8. Subject agrees not to donate blood from screening through Day 270. 9. Female subjects must be of non-childbearing potential* OR must use an acceptable method of contraception** from 28 days before prime vaccination until at least 3 months after the last vaccination. *Surgically sterile via tubal ligation, bilateral oophorectomy, hysterectomy or postmenopausal for > / = 1 year. **Abstinence (defined as refraining from heterosexual intercourse), monogamous relationship with vasectomized partner, barrier methods such as male or female condoms with spermicide or diaphragms with spermicide, intrauterine devices, and licensed hormonal methods (such as birth control pills, skin patches, Implanon(R), Nexplanon(R), DepoProvera(R), or NuvaRing(R)). 10. Male subjects must be surgically sterile via vasectomy OR must use an acceptable method of contraception* from prime vaccination until at least 3 months after the last boost vaccination Abstinence (defined as refraining from heterosexual intercourse), or condoms with spermicide. 11. Subjects must have consistent access to the internet to perform electronic data entry Has a previous HEV infection or chronic liver disease. 2. Has received any experimental agent* within 30 days prior to first vaccination, or the expected recipient of any experimental agent during this trial-reporting period. *Including vaccines, drugs, biologics, devices, and/or blood products. 3. Female subject is pregnant (or has a positive pregnancy test prior to vaccination) or breast feeding, or planning to become pregnant within 3 months after the last boost vaccination. 4. Fever (> / = 38.0 Degrees Celsius / 100.4 Degrees Fahrenheit) or other acute illness within 3 days prior to first vaccination. 5. Infection requiring systemic antibiotics or antiviral treatment within the 7 days prior to first vaccination. 6. Has a positive urine drug screen for amphetamines*, cocaine, opiates, or phencyclidine. *Prescription amphetamines are not exclusionary. 7. Chronic, clinically significant medical or psychiatric conditions* that, in the opinion of the investigator, may pose additional risk to the subject if she/he participates in the study. *Permissible conditions but are not limited to mild, well-controlled asthma, well-controlled depression, well-controlled anxiety, seasonal allergies, and well-controlled hypertension. 8. Receipt of immunosuppressive drugs*,**,*** or biologic agents within the 30 days prior to enrollment. *This includes use of oral or parental prednisone. This also includes allergy desensitization injections from 14 days prior to each vaccination through 14 days after each vaccination. The use of topical steroids for mild uncomplicated dermatitis permissible after therapy is completed. Over-the-counter (OTC) corticosteroid nasal sprays for allergic rhinitis are permissible. The use of low or moderate dose inhaled steroids is permissible. Doses are defined as per age as using inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published in **Receipt of systemic, prescription medications for the treatment of chronic medical conditions or variations of normal physiologic functions may be permissible if, in the opinion of the investigator, they are used for conditions that are not clinically significant and would not impact the safety of the subject or the safety and immunogenicity outcomes of the protocol. ***Use of systemic, over-the-counter medications and PRN systemic, prescription medication may be allowed if, in the opinion of the investigator, they pose no additional risk to subject safety or assessment of immunogenicity/reactogenicity. 9. Has known neoplastic disease* anticancer therapy, or radiation therapy within 3 years prior to first study vaccination. *Excluding non-melanoma skin cancer, such as squamous cell skin cancer or basal cell skin cancer, cured by surgical excision. 10. Has a history of any hematologic malignancy at any time. 11. Has a known or suspected congenital or acquired disease that impairs the immune system, including functional asplenia or immunosuppression as a result of underlying illness or treatment. 12. Has prior organ and/or stem cell transplant. 13. Has a history of abuse of alcohol or drugs that, in the opinion of the investigator, may interfere with the subject's ability to comply with the protocol. 14. Has behavioral or cognitive impairment or psychiatric conditions that, in the opinion of the investigator, may interfere with the subject's ability to participate in the trial. 15. Has received blood products or immunoglobulin within six months prior to vaccination. 16. Travel to Asia, the Middle East, Africa, or Central America or to an area with an active Hepatitis E outbreak* within the last 90 days or intention to travel to such areas during the study. *Outbreaks within the last 3 years. 17. Receipt of any inactivated vaccine from 2 weeks prior to each vaccination through 2 weeks after each vaccination. 18. Receipt of any live vaccine from 4 weeks prior to each vaccination through 4 weeks after each vaccination. 19. Known hypersensitivity or allergy to aluminum, any component of the vaccine, or other serious adverse reactions to vaccines or vaccine products. 20. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study. 21. Any condition that, in the opinion of the investigator, might interfere with assessing the study objectives | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 12.0-999.0, Cutaneous Leishmaniasis, American and exlusion Gender: Male or female Age: >12 yrs of age Presentation: 1-to-2 ulcerative lesions, each < 30 mm in largest diameter and with a total lesion area <900 mm2 Parasitology: Parasitological confirmation of the lesion will be made by visualization or culture of Leishmania from the biopsy or aspirate of the lesion Previous treatment for leishmaniasis No specific or putatively specific therapy (Sb, pentamidine, amphotericin B, miltefosine, imidazoles, allopurinol) in the last 3 months Other diseases: No concomitant diseases by history that would be likely in the PI's opinion to interact, either positively or negatively, with treatment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 3.0-65.0, Acute Lymphocytic Leukemia Subjects with acute lymphocytic leukemia who voluntarily signed informed consent and met the following 1. Patients with relapsed and refractory acute B lymphocytic leukemia with any of the following: 1. Recurrence after remission by chemotherapy or autologous stem cell transplantation (including B-ALL patients with bone marrow recurrence of morphology and recurrence of micro-residual ); 2. Primary B-ALL patients who cannot be completely relieved by repeated chemotherapy twice or more; 3. High-risk initial onset B-ALL patients not completely relieved after 1 or 2 times of chemotherapy but not suitable for re-chemotherapy ; 2. Tumor cells confirmed CD19 positive by Flow cytometry (FCM) 3. For B-ALL patients with simple extramedullary recurrence , there must be at least one evaluable lesion; 4. Eastern Cooperative Oncology Group (ECOG) ≤ 2 points; 5. Age 3 years old; 6. The bone marrow tumor load value (morphology) > 5% at the time of enrollment; 7. The main organ function needs to meet the above conditions: cardiac ultrasound or multiple gated image acquisition analysis （MUGA） scan indicate the cardiac ejection fraction is ≥50% , and there is no obvious abnormality in the electrocardiogram; blood oxygen saturation≥90%; creatinine ≤1.6mg/dl; alanine amino transferase (ALT) and Aspartate transaminase (AST)≤3 times normal range, total bilirubin（TBil） ≤2.0mg/dl; 8. The expected survival time is longer than 3 months; 9. The pregnancy test for women of childbearing age must be negative; Subjects with a pregnancy plan must agree to take contraception before the enrollment study and after the study lasts for one year; if the subject is pregnant or suspects of pregnancy, the investigator should be notified immediately 10. An informed consent form is required Severe cardiac insufficiency; 2) A history of severe pulmonary dysfunction; 3) Combined with other malignant tumors; 4) Combined with serious infections or persistent infection and cannot be effectively controlled; 5) Combined with metabolic diseases (except DM); 6) Combined with severe autoimmune diseases or congenital immune defects; 7) Active hepatitis (HBV DNA or detection positive); 8) HIV infection or syphilis infection; 9) A history of severe allergies to biological products (including antibiotics); 10) Subjects with recurrence after allogeneic hematopoietic stem cell transplantation 11) chronic lymphocytic leukemia（CLL） /myeloproliferative neoplasms with acute lymphoid transformation or CLL transform to ALL ; 12) Any drug that has been used against graft-versus-host disease（GVHD） for nearly 4 weeks, such as methotrexate or other chemotherapeutic drugs, mycophenolate mofetil, immunosuppressive antibodies, etc.; 13) Subjects who have received any anti-CD19 medication; 14) Subjects who have used anti-cluster of differentiation antigen 20（CD20） drugs (such as rituximab) for nearly 4 weeks; 15) Subjects who have participated in any other clinical drug trials in the past six months; 16) Female patients who are pregnant and lactating, or have a pregnancy plan within 12 months; 17) The investigator believes that it may increase the risk of the subject or interfere with the outcome of the test (with a history of severe mental illness, drug abuse and history of addiction). Exit criteria： 1. The subjects request to withdraw from the study before CAR-T infusion 2. The subjects seriously violate the protocol 3. Before CAR-T infusion, the following indicators are still abnormal after treatment: Platelets <20x10^9/L, hemoglobin ≤80g/L, peripheral finger oxygen <90%, AST / ALT / alkaline phosphatase（ALP） ≥ 2.5 upper limits of normal（ULN）, total bilirubin ≥ 1.5ULN , creatinine clearance rate <70ml / min, left ventricular ejection fraction <50%, the researcher judged that the test needs to be terminated early; 4. The therapeutic dose of steroids was not stopped within 72 hours prior to CAR-T infusion and the investigator determined that the trial needs to be terminated . However, the following physiologically acceptable doses of steroids are permissible: hydrocortisone or equivalent <6-12 mg/m2/day ; 5. Not enough T cells for manufacture standard CAR-T cells 6. Other serious adverse events occurred 7. MRD become negative after preconditioning regiment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lung Cancer Age > 18 years Indication for endoscopic sampling of suspected malignant lymphadenopathy or pulmonary lesion Written informed consent High risk conditions for the performance of bronchoscopy and/or EBUS-TBNA High risk condition for deep sedation (ASA 4) Pregnancy | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Kawasaki Disease Atypical Kawasaki Disease Affected children will be recruited if the treating clinician has made a diagnosis of possible Kawasaki disease (even if they do not fulfil the below for Kawasaki disease). The current standard diagnostic for KD (Circulation 2001 103 335-336 doi: 10.1161/01.CIR 103.2.335) are: The presence of fever for at least five days plus four of the following 1. Changes in the peripheral extremities Acute: erythema and oedema of hands and feet Convalescent: membranous desquamation of fingertips 2. Polymorphous exanthema 3. Bilateral painless bulbar conjunctival injection without exudate 4. Changes in lips and oral cavity: erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae 5. Cervical lymphadenopathy (>1.5cm diameter), usually unilateral Patients meeting not all of these may meet the for atypical Kawasaki disease, ie. if they have fever and two or three of the above and elevation of CRP or echocardiographic evidence of coronary artery dilatation. Parents of affected child must be biological parents children who do not have a diagnosis of possible Kawasaki disease | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Liver Cirrhoses older than 18 years And signed informed consent And planned either a) liver transplantation as a recipient; or b) liver transplantation as a donor any absolute/relative contraindication of contrast-enhanced MRI | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Syncope Over 18 years Diagnosis of neurally mediated syncope with a tilting table test (Tilt test) that demonstrates a mixed (type 1) or cardioinhibitory response (Type 2A and 2B) Negative impact on work and social life Non-respondent to pharmacological therapy (Fludrocortisone 0.1mg / 24 hours for 3 months) and non-pharmacological (exercise, hydration and consumption of more than 3 months) is due to a cardiologist who has performed a strict stricture over time At least 2 episodes of syncope in the last year Complete atrioventricular block Second degree ventricular atrial block Bradycardia syndrome tachycardia Disease of the sinus node Arrhythmia (bradycardia or tachycardia that generate syncope and / or low cardiac output) Syncope due to hypersensitivity of the carotid sinus Syncope with Tilt Test that demonstrates depressant vasopressor response (type 3) Refusal of the patient, his relatives or the attending physician to participate in the study | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Alcohol Use Disorder Alcohol Dependence Be at least 18 years of age. 2. Have a current (past 12 months) DSM-5 diagnosis of AUD (4 or more symptoms) assessed using the MINI neuropsychiatric interview version 7.0.2 (at least moderate severity, ICD-10-CM Code F10.20 alcohol dependence, uncomplicated). 3. Have a BAC by breathalyzer equal to 0.000 when s/he signed the informed consent document (either just prior to or immediately after signing consent). 4. Be seeking treatment for problems with alcohol reduction in drinking. 5. Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol. 6. Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal: 1. oral contraceptives, 2. contraceptive sponge, 3. patch, 4. double barrier (diaphragm/spermicidal or condom/spermicidal), 5. intrauterine contraceptive system, 6. etonogestrel implant, 7. medroxyprogesterone acetate contraceptive injection, 8. complete abstinence from sexual intercourse, and/or 9. hormonal vaginal contraceptive ring. 7. Be able to take intranasal investigational products and be willing to adhere to the investigational product regimen. 8. Complete all assessments required at screening and baseline. 9. Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing by Study Week 14. 10. Not anticipate any significant problems with transportation arrangements or available time to travel to the study site by Study Week 14. 11. Not have any plans to move within Study Week 14 to a location which would make continued participation in the study impractical. 12. Not have any unresolved legal problems that could jeopardize continuation or completion of the study. 13. Provide contact information of someone, such as a family member, spouse, or significant other, who may be able to contact the subject in case of a missed clinic appointment. 14. Be someone who in the opinion of the investigator would be expected to complete the study protocol. 15. Agree to the schedule of visits, verbally acknowledge that s/he will be able to attend each scheduled visit, participate in phone visits and that s/he does not have any already scheduled events or a job that may substantially interfere with study participation. 16. If taking a medication for depression or anxiety, must have been taking a stable dose in the 2-months prior to randomization and plan to continue during the study. This includes drugs such as the following SSRIs Dual uptake inhibitors SNRIs Tricyclic antidepressants MAOIs Bupropion 17. Not currently taking oxytocin and agree not to take non-study oxytocin for the duration of the study Contact study site for | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Richter Syndrome Diffuse Large B Cell Lymphoma Follicular Lymphoma Indolent Non-hodgkin Lymphoma Loss of Chromosome 17p Lymphoplasmacytic Lymphoma Marginal Zone Lymphoma TP53 Gene Mutation Diagnosis of Richter syndrome (RS; transformed CLL), or indolent non-Hodgkin's lymphoma (NHL) (follicular lymphoma [FL], lymphoplasmacytic lymphoma [LPL], marginal zone lymphoma [MZL]) in transformation. Only patients who have diffuse large B-cell lymphoma (DLBCL) histology are eligible Participants with RS must have received at least 2 cycles of prior systemic therapy for either RS or underlying CLL Participants with FL and other indolent lymphomas in transformation must have underwent ≥ 1 prior chemo-immunotherapy regimen (e.g., R-CHOP or similar) administered for ≥2 cycles and have had either documented disease progression to the most recent treatment regimen, or refractory disease and must not be candidates for or planning to pursue autologous stem cell transplant, or must have relapsed following autologous stem cell transplant which took place at least 3 months prior to study therapy Radiographically measurable lymphadenopathy (>= 1.5 cm) or measurable extra-nodal disease Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Direct bilirubin =<2 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than 2.5 x institutional ULN Estimated creatinine clearance (CrCL) using the Cockcroft-Gault equation >= 50 mL/min or creatinine < 1.5 mg/dL Platelets >= 75,000/mm^3 (>=25,000/mm^3 if due to disease involvement in the bone marrow Absolute neutrophil count >= 1000/mm^ (>= 500/mm^ if due to disease involvement in the bone marrow Female participants who History of allogeneic bone marrow or organ transplant Prior therapeutic intervention with any of the following Therapeutic anti-cancer antibodies within 4 weeks Radio or toxin-immunoconjugates within 10 weeks All other chemotherapy, radiation therapy within 30 days prior to initiation of study therapy Targeted therapy within 6 half-lives (for example, 36 hours for ibrutinib) History of prior malignancy except Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Chronic Lymphocytic Leukemia Recurrent Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Richter Syndrome Small Lymphocytic Lymphoma Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma Diagnosis of CLL or small lymphocytic lymphoma (SLL) meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 AND biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), clinically consistent with Richter?s syndrome (RS) OR histologically diagnosed relapsed or refractory DLBCL including transformed follicular lymphoma (tFL) ineligible for or refractory to platinum containing salvage therapy for the dose escalation portion of the study. For the dose expansion phase only patients with CLL with transformation to DLBCL or tFL will be eligible Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count (ANC) >= 500/uL Platelet count >= 30,000/uL (unless due to bone marrow involvement) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 ULN Total bilirubin =< 1.5 ULN (unless due to liver involvement, hemolysis, or Gilbert?s disease) Creatinine clearance >= 40 mL/min (Cockcroft-Gault estimated) Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study Patients must sign an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study Documented infection with human immunodeficiency virus (HIV) or chronic, active hepatitis B or C infection Any chemotherapy or monoclonal antibodies within 14 days or kinase inhibitors (except BTKi) within 5 half-lives before cycle 1, day 1 (C1D1). BTK inhibitors may be continued until 2 days prior to C1D1. Steroids are allowed for palliation of symptoms due to lymphoma Toxicity from previous therapy which has not resolved to grade 1 (or patient?s previous baseline) Other active malignancies except those treated with curative intent with no active disease at the time of study entry or those felt to be at low risk of progression or recurrence over the next 2 years (such as low risk prostate cancer on active surveillance) New York Heart Association (NYHA) class III/IV heart disease or other significant medical condition or organ system dysfunction which could compromise the subject?s safety or put the study outcomes at undue risk Uncontrolled systemic infection Unable to swallow capsules or significant malabsorption syndrome, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction at the time of screening Patients who are pregnant or breastfeeding Patients with known central nervous system (CNS) involvement by CLL or lymphoma Patients who have underwent autologous or allogeneic stem cell transplant =< 4 weeks prior to C1D1 or have active graft-versus-host disease are excluded | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Richter Syndrome Entry for randomised trial component (standard of care and experimental arms): for the randomised trial component Suitable for anthracycline-containing chemo-immunotherapy Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS ECOG performance status of 0, 1, 2 or 3 Age 16 years and over Signed written informed consent prior to performing any study-specific procedures for the randomised trial component Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation. (Please note that pre-treatment with prednisolone up to 2mg/kg is allowed for up to 14 days prior to the start of treatment) Ibrutinib-exposed CLL patients who have been newly diagnosed with RS within four weeks of their last dose of ibrutinib. (Ibrutinib-exposed CLL patients who discontinue ibrutinib due to toxicity or progressive CLL and later (more than four weeks) develop RS are not excluded from the randomised trial component) Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted, with the exception of patients who have progressed on ibrutinib see criterion above) Known central nervous system (CNS) involvement of CLL or DLBCL Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded Known human immunodeficiency virus (HIV) positive | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Hemophilia B Have a diagnosis of haemophilia B Have started Alprolix treatment prior to enrolment visit, or at enrolment prescribed treatment with Alprolix irrespective of participation in the study Signed and dated informed consent provided by the patient, or the patient's legally acceptable representative for patients under the legal age, before any study-related activities are undertaken. Assent should be obtained from paediatric patients according to local regulations Participation in an investigational medicinal product trial at enrolment visit | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.083-18.0, Kawasaki Disease Appendicitis Patients with Kawasaki disease Acute abdomen requiring surgery Patients with chronic gastrointestinal disease Incomplete data on the charts | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Lymph Node Disease Imaging examination indicates enlarged intrathoracic lymph nodes need pathological diagnosis (any lymph node has a short diameter > 1 cm in CT or PET-CT SUV value > 2.5). 2. Accessible mediastinal and hilar lymphadenopathy to EBUS-TBNA. 3. Inform consent signed Contraindications of EBUS-TBNA. Such as use of anticoagulant therapy or presence of a coagulopathy (platelet count < 50000 or INR > 1.5). 2. Severe cardiopulmonary dysfunction and other indications that can't tolerate bronchoscopy. 3. Life expectancy less than 6 months. 4. Uncooperative patients. 5. Patients representing vulnerable populations (prisoners, pregnant women, etc). 6. Researchers consider it inappropriate to participate in this study | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 20.0-80.0, Chronic Phase Chronic Myelogenous Leukemia Newly diagnosed CML patients 2. Receive TKI treatment (imatinib, nilotinib, dasatinib) selected among those admitted to the investigator's hospital. 3. Ageing group 20yr up to 80 yr CML patients who previously treated with TKI. 2. Age below 20 yrs | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 1.0-31.0, B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma Down Syndrome All B-ALL patients must be enrolled on APEC14B1 and consented to Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731 Age at diagnosis Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS) Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS) Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS) B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment) B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment) Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731 For patients receiving steroid pretreatment, the following additional apply Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis Patients who have received > 72 hours of hydroxyurea B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells Patient must not have acute undifferentiated leukemia (AUL) Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment) Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Richter Syndrome Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma according to the revised iwCLL criteria19 with biopsy proven transformation to diffuse large B-cell lymphoma, consistent with RS according to the 2016 WHO classification Both patients with previously treated or treatment-naïve CLL are eligible Age greater than or equal to 18 years Eastern Cooperative Oncology Group (ECOG) performance status <3 Patients must meet the following hematologic at screening, unless they have significant bone marrow involvement of either CLL or RS cells confirmed on biopsy: absolute neutrophil count ≥1.0 G/L, platelet count ≥50 G/L independent of transfusion within 7 days of screening Subject must have adequate coagulation, renal, and hepatic function at screening Adequate left ventricular ejection function (> 50 %) Patients who have undergone prior allogeneic hematopoietic stem-cell transplantation (HSCT) are eligible as long as they do not have significant active graft versus host disease and that their transplant day 0 is > 6 months from their first dose of protocol therapy Female patients of child bearing potential must have negative pregnancy test and use an effective method of birth control during treatment period and 48h thereafter; Males must use an effective method of birth control during treatment period and 48h thereafter Ability to understand and the willingness to sign a written informed consent document Patients with the Hodgkin variant of RS Patients with previously treated RS History or presence of clinically relevant disorder affecting the central nervous system (CNS) Known active DLBCL in the CNS (confirmed by cerebrospinal fluid analysis) Steroids treatment (≥ 20 mg for one week) before HSCT within 6 months before Active graft-versus-host disease History of other malignancies, except: i) malignancy treated with curative intent and with no recurrence over the last 5 years ii) adequately treated non-melanoma skin cancer without evidence of disease iii) adequately treated carcinoma in situ without evidence of disease History of human immunodeficiency virus Hepatitis B or C seropositivity (unless clearly due to vaccination) | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-130.0, Phase I: Relapsed or Refractory B-cell Malignancies Phase II Cohort A: Relapsed or Refractory Mantle Cell Lymphoma Phase II Cohort B: Relapsed or Refractory Chronic Lymphocytic Leukemia Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Chinese subjects at least 18 years of age at the time of study entry. 3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 4. Adequate hematological and organ function. 5. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy. 6. Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14) (q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5). Disease had relapsed after or been refractory to previous treatment. 7. Diagnosis of CLL that meets published diagnostic criteria. Must have received ≥ 1 prior systemic therapies for CLL. 8. Active disease per iwCLL 2018 that requires treatment. (CLL only) 9. Other relapsed/refractory B-cell malignancies without stand of care (phase 1 only) Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to <2 years. 2. Significant cardiovascular disease. 3. Known central nervous system involvement of lymphoma/leukemia or leptomeningeal disease. 4. Known history of HIV, serologic status reflecting active hepatitis B or C infection. 5. Major surgery within 4 weeks before first dose of study drugs. 6. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura. 7. Required or received anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon). 8. Prior exposure to a BCR or BCL-2 inhibitor. 9. Use of a strong inhibitor or inducer of CYP3A. 10. Breastfeeding or pregnant | 2 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-999.0, Melanoma Subjects must have histologically proven, malignant melanoma, that is advanced (stage IV) or is unresectable and therefore considered surgically incurable Subject's disease must be measurable by immune-related using clinical assessments or imaging Subjects must have at least one (1), but preferably two (2), sites of readily accessible, superficial disease (i.e., cutaneous, subcutaneous, and/or readily-palpable lymphadenopathy) that are amenable to repeated hu14.18-IL2 injections and two (2) to four (4) biopsies (designated Lesions A (index lesion) and B). These lesions must be at least 1 cm, but no greater than 5 cm, in longest diameter If there are two lesions, one will be injected with hu14.18-IL2 and undergo biopsies. The second will not undergo injections with hu14.18-IL2, but will undergo two biopsies and be observed clinically. It is preferable, but not required, that these lesions have not received prior RT Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Subjects must have received or declined at least one FDA approved immunotherapy treatment demonstrating an impact on survival (i.e: anti-CTLA-4 antibody, anti-PD-1 antibody, IL2, etc) Subjects with Central Nervous System (CNS) metastases are eligible if the CNS lesions are stable for at least 2 months and if tapered off treatment doses of systemic corticosteroids for at least 2 weeks prior to enrollment on the trial. Management with maintenance physiologic doses of corticosteroids is acceptable Subjects to be entered into Phase IB, IC and ID must be evaluated by a radiation oncologist and determined to have a need for palliative RT based on current or imminent symptoms at a tumor site that is also injectable. If palliative RT is needed to one or more disease sites, a separate site of disease that does not require RT must remain to enable assessment of systemic disease response Subjects must have adequate bone marrow, liver, and renal function as defined by Total White Blood Cell (WBC) > 3,000/mm3 (or total neutrophil count > 1,500/mm3), platelets >100,000/mm3, and hemoglobin > 10 g/dL Subjects with a diagnosed auto-immune disease (exceptions: subjects with controlled diabetes mellitus type I, thyroid disease, vitiligo and alopecia areata not requiring treatment with immunosuppressants are eligible) Subjects with a history of diabetes mellitus requiring systemic therapy within the past 3 months (i.e. either oral hypoglycemic agents or insulin) must have a documented Hemoglobin A1c <8.0% at the time of enrollment Subjects with known genetic conditions causing pre-disposition to RT toxicity (i.e: Li-Fraumeni, ATM deficiency, active scleroderma, etc) Subjects who cannot provide independent, legal, informed consent Women of childbearing potential will be excluded if they are pregnant, nursing, or not willing to use effective contraception, as discussed with the treating physician, during the treatment period. A negative pregnancy test (serum or urine) is required for women of child bearing potential within 14 days before study registration A person of childbearing potential is anyone (regardless of sexual orientation, gender identity, having undergone tubal ligation, or remaining celibate by choice) who was born with a uterus and at least one ovary and meets the following Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had a menses at any time in the preceding 12 consecutive months) Subjects with symptoms of ischemic cardiac disease, congestive heart failure, or myocardial infarction within the immediate preceding 6 months and/or uncontrolled cardiac rhythm disturbance Subjects with significant psychiatric disabilities or seizure disorders | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 1.0-24.0, B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma Central Nervous System Leukemia Mixed Phenotype Acute Leukemia Testicular Leukemia B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 7 business days after enrollment for MPAL patients. If not performed within this time frame, patients will be taken off protocol APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732 White blood cell count (WBC) for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy) Age 1-9.99 years: WBC >= 50,000/uL Age 10-24.99 years: Any WBC Age 1-9.99 years: WBC < 50,000/uL with Testicular leukemia CNS leukemia (CNS3) Steroid pretreatment White blood cell count (WBC) for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy) Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group) With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732 Patients who have received > 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells Patients with acute undifferentiated leukemia (AUL) are not eligible For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional apply T-lymphoblastic lymphoma Morphologically unclassifiable lymphoma Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 0.0-999.0, Lung Cancer Metastatic Nodes, Lung Suspected and later on confirmed lung cancer Presence of at least one mediastinal lymph node measuring > 10 mm in short diameter on computerised Tomography Age <18 History any malignancy apart from non-melanomatous skin cancer Inability to give informed consent | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Chronic Lymphocytic Leukemia Men or women ≥ 18 years and ≤ 75 of age. 2. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria. 3. Treatment-naive patients. Those patients received short-term substandard treatment are permitted if meet all the items listed below: 1. Untreated with combined chemotherapy such as CHOP ,COP and so on. 2. Unteated with chemotherapy regimens including fludarabine and bendamustine. 3. Unteated with Ibrutinib. 4. If treated with chlorambucil or cyclophosphamide,should less than 3 weeks. 5. If treated with interferon, should less than 6 months. 6. No objective response are achieved (PR or CR). 4. CLL/SLL requiring treatment as defined by at least one of the following 1. Development of, or worsening of, anemia to Hb<100g/L (non-hemolytic) . 2. Development of, or worsening of, thrombocytopenia to PLT<100,000/L. 3. Massive (≥ 6 cm below left costal margin), progressive or symptomatic splenomegaly. 4. Massive nodes (≥ 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy . 5. Progressive lymphocytosis with an increase of > 50% over a 2-month period or lymphocyte-doubling time of < 6 months. Lymphocyte-doubling time may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30,000/L, LDT should not be used as a single parameter to define treatment indication. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL/SLL (eg, infection, use glucocorticoid) should be excluded. f)Symptomatic or functional extranodal sites involved s (eg. Skin,kidney, lungs and so on). g)Constitutional symptoms, defined as any 1 or more of the following disease-related symptoms or signs: i. Unintentional weight loss of ≥ 10% within the previous 6 months ii.Significant fatigue (ie, inability to work or perform usual activities) 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6. Expected to survival period for 3 months or more History of malignant tumour except CLL in the past 1year(including active central nervous system (CNS) involvement with lymphoma). 2. Transformed to large cell lymphoma manifested by clinical evidence, or progressed to prolymphocytic leukemia(PLL). 3. Have active autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, and require treatment. 4. Inadequate hepatic and renal function defined as: AST and ALT >4.0 x upper limit of normal (ULN), bilirubin >2.0 x upper limit of normal (ULN), Adequate renal function defined by serum creatinine >1.5 x upper limit of normal (ULN),unrelated to lymphoma. 5. Severe or uncontrolled infection. 6. Central nervous system (CNS) dysfunction with clinical manifestation. 7. Other serious medical diseases that may affect the study（eg. Uncontrolled diabetes, gastric ulcer, other severe cardiopulmonary disease),and final decided by the investigator. 8. Ongoing and uncontrolled bleeding 9. History of major life-threatening bleeding, especially due to irreversible cause. 10. Requirement for continuous anticoagulation drugs. 11. Major surgery within 30 days(excluding lymph node biopsy). 12. Pregnant or Lactating women, or women of reproductive age refusal to take contraceptive measures. 13. Allergy to any drug used in the study | 1 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-75.0, Hepatic Encephalopathy Acute-On-Chronic Liver Failure Age 18-75 years Patients with ACLF with presence of hepatic encephalopathy > grade 2 as per WHC Pregnant women or those who are suspected to be having acute fatty liver of pregnancy Malarial hepatopathy, enteric hepatitis, or ischemic hepatitis Serum Na <125 mEq/litre Gastrointestinal (GI) obstruction, ileus, or gastric retention Bowel perforation Toxic colitis or toxic megacolon Structural brain lesions (as indicated by computed tomography imaging if available and confirmed by neurological exam) Other causes of altered mental status (i.e. not meeting the definition of hepatic encephalopathy Uncontrolled infection with hemodynamic instability requiring vasopressors | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 1.0-18.0, Health Care Associated Infection Hand Hygiene All intraoperative providers at Children's Hospital Colorado will be eligible to participate 2. Pediatric patients age 1-18 years old presenting to the main operating room at Children's Hospital Colorado who will require general anesthesia with placement of a peripheral intravenous catheter Adult patients, age greater than 18 years old 2. Patients without an intravenous catheter | 0 |
This is a 57-year-old gentleman with CLL and large cell transformation. He presented with his disease back in [**10/2119**] with an elevated white count and LDH. He was without any splenomegaly or any cytopenias at that time. He did have some bulky lymphadenopathy. He then completed four cycles of FCR therapy, which he completed back in 09/[**2119**]. He had an excellent response to therapy and was monitored off treatment for approximately two years. He then presented in [**7-/2122**] with a rising white count, approximately 50% lymphocytes, and a mildly elevated LDH. He also had some mild worsening palpable lymphadenopathy. He then received four cycles of PCR, but did not have much in the way of response and his treatment regimen was switched to R-CVP of which he received two cycles. He did again not have a significant response, though continued to have an excellent performance status, and he was ultimately switched to Campath therapy. He did have resolution of his lymphocytosis, and his white count has come down nicely, but did not have much in the way of response in terms of reducing his bulky lymphadenopathy. He then eventually had developed an enlarging left cervical node which was biopsied and | eligible ages (years): 18.0-130.0, Chronic Lymphocytic Leukemia Men and women ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) 2. Diagnosis of CLL that meets published diagnostic (Hallek et al. 2018): 1. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥1 B-cell marker (CD19, CD20, and CD23) and CD5 2. Prolymphocytes may comprise <55% of blood lymphocytes 3. Presence of ≥5 × 109 B lymphocytes/L (5000/μL) in the peripheral blood (at any point since the initial diagnosis) 3. Active disease as per at least 1 of the following IWCLL 2018 1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <10 g/dL) and/or thrombocytopenia (platelets <100,000/μL). 2. Massive (i.e., ≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly. 3. Massive nodes (i.e., ≥10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy 4. Progressive lymphocytosis with an increase of >50% over a 2-month period or a lymphocyte doubling time (LDT) of <6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte count obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of <30x109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded. 5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy 6. B-symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥1 of the following disease-related symptoms or signs: o Unintentional weight loss ≥10% within the previous 6 months before screening o Significant fatigue (Eastern Cooperative Oncology Group [ECOG] performance status ≥2; inability to work or perform usual activities) o Fevers higher than 100.5°F or 38.0°C for ≥2 weeks before screening without evidence of infection o- Night sweats for ≥1 month before screening without evidence of infection 4. Must meet 1 of the following a. Have received no prior therapy for treatment of CLL and meets 1 of the following i. A score of >6 on the Cumulative Illness Rating Scale (CIRS) ii. Creatinine clearance of 30 to 69 mL/min using the Cockcroft-Gault equation b. Have previously received therapy for CLL and have either refractory or relapsed CLL c. Have received prior BTKi therapy (i.e., defined as a subject who discontinued a BTKi for any reason except disease progression) for CLL d. Criterion deleted. 5. ECOG performance status of ≤2 6. Female subjects of childbearing potential (i.e., not surgically sterile or postmenopausal) who are sexually active with a non-sterilized male partner must use ≥1 highly effective method of contraception from the time of screening and must agree to continue using such precautions for 2 days after the last dose of study treatment. Contraception measures and restrictions on sperm donation are not required for male subjects. 7. Fluorescence in situ hybridization (FISH) within 60 days before or during screening reflecting the presence or absence of del(17p), 13q del, 11q del, and trisomy of chromosome 12 along with the percentage of cells with the deletion, along with TP53 sequencing. Subjects must also have molecular analysis to detect IGHV mutation status at any time point since diagnosis. 8. Each subject (or legally authorized representative if allowed per local regulations) must be willing and able to adhere to the study visit schedule, understand and comply with other protocol requirements, and provide written informed consent and authorization to use protected health information Subjects who have had disease progression while on a BTKi for any malignant or nonmalignant condition 2. Prior malignancy (other than CLL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, early stage prostate cancer, or other cancer from which the subject has been disease-free for ≥2 years 3. History of confirmed progressive multifocal leukoencephalopathy 4. Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months before screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval using Fridericia's formula (QTcF) >480 msec at screening. Note: Subjects with rate-controlled, asymptomatic atrial fibrillation are allowed to enroll in the study. 5. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass. 6. Evidence of active Richter's transformation. If Richter's transformation is suspected (i.e., lactate dehydrogenase [LDH] increased, asymmetric fast lymph node growth or clinical suspicion), it should be ruled out with positron emission tomographycomputed tomography (PET-CT) and/or biopsy according to guidelines. 7. Central nervous system (CNS) involvement by CLL. 8. Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are on ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment. 1. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus PCR result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded. 2. Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enroll.lment. Those who are hepatitis C virus PCR positive will be excluded 9. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (>20 mg daily of prednisone or equivalent for longer than 2 weeks). 10. History of stroke or intracranial hemorrhage within 6 months before the first dose of study treatment. 11. History of bleeding diathesis (e.g., hemophilia or von Willebrand disease) 12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening. 13. Major surgical procedure within 4 weeks before first dose of study treatment. Note: Subjects who have had major surgery must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study treatment. 14. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study. 15. All subjects requiring or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days before first dose of study treatment. 16. Absolute neutrophil count (ANC) <0.50 x 109/L or platelet count <30 x 109/L, unless proven due to CLL and raised above the limits by granulocyte colony-stimulating factor (G-CSF) therapy and/or pooled platelet transfusion 17. Total bilirubin >3.0x upper limit of normal (ULN); or aspartate aminotransferase or alanine aminotransferase >3.0x ULN. Exception will be for Gilbert syndrome; if an investigator feels that a subject's total bilirubin is elevated secondary to Gilbert's, the subject must have a documented unconjugated bilirubin being >80% of the total bilirubin number. The investigator must also document that hemolysis has been ruled out along with (near)-normal lactate dehydrogenase and haptoglobin 18. Estimated creatinine clearance of <30 mL/min, calculated using the formula of Cockcroft and Gault or by direct assessment (i.e., creatinine clearance or ethylene diamine tetra-acetic acid (EDTA) clearance measurement) 19. Breastfeeding or pregnant 20. Received any chemotherapy, external beam radiation, investigational drug, or any other anti-CLL therapy within 30 days before first dose of study treatment 21. Concurrent participation in another therapeutic clinical study 22. History of interstitial lung disease 23. Requiring long-term (> 1 week) treatment with a strong cytochrome CYP3A inhibitor/inducer. In addition, the use of strong or moderate CYP3A inhibitors or inducers within 7 days of the first dose of study drug is prohibited | 1 |
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