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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): 18.0-999.0, Lung Cancer Non Small Cell Lung Cancer Adenocarcinoma of Lung Participants are eligible to be included in the study only if all of the following apply Male and female participants who are at least 18 years of age on the day of signing the informed consent will be enrolled in the study Subjects must have histologically confirmed diagnosis of non-squamous non-small cell lung cancer not amenable to potentially curative treatments (surgical resection, definitive radiation therapy or a combined modality approach) or targeted agents to actionable EGFR mutations or ALK or ROS1 gene rearrangement and excluding neuroendocrine tumors. Activating KRAS mutations are allowed. The diagnosis must be confirmed by the Laboratory of Pathology, CCR, NCI. Mutation confirmation may be done by referring institutions or by one of the assays in the Protocol Have provided archival tumor tissue sample or newly obtained fresh core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue Histologically confirmed 25% of tumor cells expressing mesothelin as determined by NCI Laboratory of Pathology. Determination can be made using archival tumor tissue or fresh biopsy Have measurable disease based on 1.1. Lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions Subjects must have received prior standard of care treatments for locally advanced or metastatic NSCLC Patients must be more than 3 weeks out of systemic treatments, such as chemotherapy All acute toxic effects of any prior radiotherapy, chemotherapy, immunotherapy, or surgical procedure must have resolved to Grade less than or equal to 1, except alopecia (any grade) and Grade 2 peripheral neuropathy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 | 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 New and existing patients seen for treatment of monoclonal B-cell lymphocytosis Any low grade lymphoproliferative disorder Chronic Lymphocytic Leukemia in the Dana Farber Cancer Institute Hematologic Oncology Clinic or elsewhere | 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): 12.0-999.0, Cystic Fibrosis Key Completed study drug treatment in parent study (VX18-445-104); or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study Key History of study drug intolerance in parent study 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): 18.0-75.0, Cochlear Prosthesis Implantation Age between 18 and 75 years inclusive Use of the second CI for at least 1 year Regular follow-up in the Ear Nose and Throat department of Edouard Herriot Hospital in Lyon Post-lingual deafness Average voice recognition over 80% with 2 Cochlear Implants Normal vision (with or without correction) Able to understand the experimental instructions Affiliated to a social security scheme Oculomotor disorder Bilateral vestibular areflexia | 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, CLL Transformation Ability to understand and the willingness to sign a written informed consent document 2. Signed Informed Consent 3. Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma as IW-CLL 2008 (Hallek et al, 2008) with biopsy proven transformation to diffuse large B cell lymphoma (DLBCL), consistent with Richter's Syndrome 4. Age greater than or equal to 18 years 5. ECOG performance status <= 2 6. Patients must meet the following hematologic at screening, unless they have significant bone marrow involvement of their malignancy confirmed on biopsy Absolute neutrophil count >=1000 cells/mm3 (1.0 x 10^9/L) Platelet count >= 50,000 cells/mm3 (50 x 10^9/L) within 7 days of screening Total hemoglobin > 9 g/dL (without transfusion support, unless anemia is due to marrow involvement of CLL) 7. Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at screening as follows Activated partial thromboplastin time (aPTT) and International normalized ratio (INR) > 1.5 x ULN for patients not receiving therapeutic anticoagulation Creatinine <= 1.5 x ULN or creatinine clearance >= 50 mL/min based on Cockcroft-Gault formula Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 × ULN Bilirubin <= 1.5 × ULN; 8. Subjects with Gilbert's Syndrome or resolving autoimmunohemolytic anemia may have a bilirubin up to 3.0 × ULN and are still eligible 9. Negative pregnancy tests as verified by the investigator prior to starting any treatment Prior treatment for Richter transformation. 2. Prior treatment with obinutuzumab anti PD-1 or PDL-1 antibodies. 3. Prior treatment with venetoclax. 4. Hypersensitivity to obinutuzumab, venetoclax or atezolizumab or their formulation excipients. 5. Patients with the Hodgkin variant transformation of CLL. 6. Prolymphocytic transformation. 7. Patients with a previous history of indolent B cell malignancies other than CLL. 8. History of other malignancy other than CLL and Richter syndrome that could affect compliance with the protocol or interpretation of results with the exception of: 1. Patients with curatively treated basal or squamous cell carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix 2. Patients with a malignancy that has been treated with surgery alone with curative intent. Individuals in documented remission without treatment for > 2 years prior to enrollment may be included at the discretion of the Sponsor-Investigator. 3. Low-risk prostate cancer on active surveillance. 9. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm). 10. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle1, Day1. 11. Clinically significant history of liver disease, including autoimmune hepatitis, current alcohol abuse, or cirrhosis. 12. Presence of positive PCR for hepatitis B, hepatitis C or positive hepatitis B surface antigen. 13. Patients with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia. 14. History of active autoimmune disease. 15. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed. 16. Concurrent systemic immunosuppressant therapy within 28 days of the first dose of study drug. 17. Corticosteroids are allowed, but must be dosed at prednisone 30 mg (or equivalent) or lower prior to the start of chemotherapy. 18. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug. 19. Known bleeding disorders (eg, von Willebrand's disease) or hemophilia. 20. Requires anticoagulation with vitamin K antagonists (e.g. phenprocoumon, warfarin) 21. History of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV). 22. Major surgery within 4 weeks of first dose of study drug. 23. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk. 24. Patients with infections requiring IV treatment (Grade 3 or 4) within the last 2 months prior to enrolment | 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, B-ALL B-cell Non Hodgkin Lymphoma DLBCL Disease Status Disease Status of ALL Must have chemotherapy refractory disease defined as progression or stable disease after two lines of therapies, or relapsed disease after achieving CR Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, polymerase chain reaction (PCR), Fluorescence in in situ hybridization (FISH), or next generation sequencing) require verification of MRD on two occasions at least 2 weeks apart Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs) Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR) are eligible. Disease Status of aggressive B-cell NHL Histologically confirmed aggressive B cell NHL including the following types defined by 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; OR transformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma to DLBCL Subjects with DLBCL or subjects with transformed follicular lymphoma (FL), marginal zone lymphoma (MZL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have not received chemotherapy prior to transformation Must have received an anthracycline regimen and an anti CD20 monoclonal antibody (unless documented CD20-negative) and be refractory or relapsed after second line of DLBCL treatment. Subjects with a partial response to second line therapy must be ineligible for autologous transplant Subjects with transformed FL, MZL, or CLL/SLL who have received anthracycline-containing chemotherapy prior to transformation Recurrent or refractory ALL limited to isolated testicular disease. 2. Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy. 3. History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD22-CAR T cells. Subjects in remission <1 year are not eligible Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible Hormonal therapy in subjects in remission > 1 year will be allowed. 4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. 5. Ongoing infection with HIV Hepatitis B (HBsAg positive) or Hepatitis C virus (HCV) (anti HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing. 6. CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity. 7. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment. 8. Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment. 9. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 10. Women who are pregnant or breastfeeding. 11. 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. 12. Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years | 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, Hemorrhoids, Internal Patients referred to proctologic consultation of Centro Hospitalar Universitário do Porto (CHUP) older than 18 years Clinical diagnosis of hemorrhoidal disease grade I, II and III (Goligher's classification) Refractory to conservative management (dietary modification, intestinal transit modifiers, topical and phlebotonic medications) for a period of no less than 4 weeks Hepatic cirrhosis Pregnant or breast-feeding women Known allergy to polidocanol Another perianal disease that can cause symptoms similar to hemorrhoidal disease Concomitant presence of external hemorrhoidal disease and/or hemorrhoidal thrombosis Office-based or surgical treatment for hemorrhoids within 6 months prior to inclusion Antiplatelet or hypocoagulant medication Inherited bleeding disorders Immunosuppressive states Inflammatory bowel 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, Clonal Hematopoiesis of Indeterminate Potential Clonal Cytopenia of Undetermined Significance Participants with Clonal Hematopoiesis of Indeterminate Significance (CHIP) Greater than or equal to 18 years of age Willingness and capacity to provide written informed consent Presence of a somatic pathogenic variant associated with hematological malignancy Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL) Presence of a cytopenia: --Hemoglobin, <10 g/dL; platelet count, <100x10(9) /L; or absolute neutrophil count, <1.5x10(9) /L Pregnant at the time of recruitment Treatment with previous chemotherapy or radiotherapy Participants with Clonal Cytopenia of Uncertain Significance (CCUS) Greater than 18 years of age Willingness and capacity to provide written informed consent Presence of a somatic pathogenic variant associated with hematological malignancy without morphological evidence of myelodysplasia and without a MDS defining cytogenetic abnormality, confirmed at NIH Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant Bone marrow aspirate and biopsy excluding hematological malignancy and MDS Presence of a cytopenia for >30 days | 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, Prostate Cancer histological confirmation of prostatic adenocarcinoma, at least two symptomatic bone secondary lesions detected by bone scan and no known visceral metastases, except for malignant lymphadenopathy with less than 3 cm in the short axis diameter Eastern Cooperative Oncology Group (ECOG) performance status (PS) score >2 and inadequate hematological, hepatic and renal function | 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, Advanced Prostate Cancer Written informed consent 2. Age ≥18 years 3. Patients with APC with predominantly bone disease confirmed by bone scan (within 6 weeks) or CT (within 6 weeks), of starting treatment (Cycle 1 Day 1). Patients with local recurrence and bone metastases with an associated soft tissue component, will be allowed into the trial. Pelvic lymphadenopathy <1.5cm in short axis is not an exclusion. 4. Systemic therapy indicated for disease progression, as clinically indicated Patient is claustrophobic. 2. Contraindications to MRI examination (e.g. cardiac pacemakers, cochlear implants). 3. Measurable soft tissue or lymph node metastases or any metastatic disease outside the bone that is measurable will be an (unless it is pelvic nodal disease <1.5cm in short axis). Bone metastases with associated soft tissue components will also not be an exclusion | 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): 65.0-999.0, Lymphoid Leukemia Non-Hodgkin's Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Histologically confirmed, non-17p del chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with any of the three following conditions No prior CLL/SLL directed therapy and Cumulative Illness Rating Scale (CIRS) score >= 7 Age >= 65 At least one prior CLL/SLL directed therapy with any CIRS score CLL/SLL requiring treatment as defined by at least one of the following based on IWCLL 2018 guidelines Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive (> 6 cm below left costal margin), progressive or symptomatic splenomegaly Massive nodes (> 10 cm in longest diameter), or progressive or symptomatic lymphadenopathy 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 < 30x10^9/L (30,000/uL), lymphocyte-doubling time 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, steroid administration) should be excluded Constitutional symptoms, defined as any 1 or more of the following disease-related symptoms or signs Presence of chromosome 17p deletion, known p53 deletion, or known p53 mutation that impairs normal function Prior treatment including systemic therapy or radiotherapy within 21 days of study initiation Prior treatment with bendamustine within 2 years Prior treatment with copanlisib Documented evidence of resistance to prior treatment with idelalisib or other PI3K inhibitors defined as: No response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or Progression (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor Active autoimmune disease or prior autoimmune disease requiring systemic immunosuppression within the past 6 months Poorly controlled diabetes mellitus defined as hemoglobin A1c > 8.5% Known lymphomatous involvement of the central nervous system Known history of human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations Hepatitis B (hepatitis B virus [HBV]) or C (hepatitis C virus [HCV]) infection. All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-deoxyribonucleic acid (DNA), these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA) | 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, Lymphoma, B-Cell Lymphoma, Non-hodgkins Chronic Lymphocytic Leukemia B-Cell Chronic Lymphocytic Leukemia Patients must have any B-cell lymphoma, or CLL/SLL, Gray-zone lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, or classical Hodgkin lymphoma with any CD19 or CD20 expression on Reed-Sternberg cells. Lower grade lymphomas or CLL transformed to DLBCL are potentially eligible as is primary mediastinal B-cell lymphoma and all other subtypes of DLBCL. Burkitt and mantle cell lymphoma are potentially eligible For classical Hodgkin lymphoma only, a biopsy from any time from any institution that shows any CD19 or CD20 expression on Reed-Sternberg cells is adequate for eligibility. CD19 or CD20 expression on the Reed-Sternberg cells that is weak or only present on some Reed-Sternberg cells by immunohistochemistry is compatible with protocol eligibility For all lymphoma types except for classical Hodgkin lymphoma, either CD19 or CD20 expression must be uniform . Uniform CD19 or CD20 expression is defined as no obvious lymphoma population lacking antigen expression is present. Antigen expression can be assessed by either immunohistochemistry or flow cytometry Only when insufficient biopsy material is available to allow CD19 and CD20 expression assessment at the NIH, CD19 and/or CD20 staining performed at another institution can be used DLBCL patients must have received at least two prior chemotherapy-containing regimens at least one of which must have contained doxorubicin and a monoclonal antibody. Follicular lymphoma patients must have received at least 2 prior regimens including at least 1 regimen with chemotherapy. All other B-cell lymphoma and leukemia patients must have had at least 1 prior chemotherapy-containing regimen. All patients with CLL or small lymphocytic lymphoma must have had prior treatment with ibrutinib or another signal transduction inhibitor.and venetoclax Hodgkin lymphoma patients must have had at least 3 prior lines of therapy documented progression of lymphoma while on checkpoint inhibitor therapy or failure to respond to checkpoint inhibitor therapy, or intolerance to checkpoint inhibitor therapy had at least 1 prior cytotoxic chemotherapy-containing regimen had prior exposure to brentuximab vedotin Patients that require urgent therapy due to tumor mass effects or spinal cord compression Patients must not have received any anti-CD20 or anti-CD19 antibody products in the past 30 days prior to CAR T-cell infusion Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with infusion of CAR-T cells within 8 weeks of enrollment Patients that have active hemolytic anemia HIV-positive patients are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these patients Patients with second malignancies in addition to their B-cell malignancy are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs Active uncontrolled systemic infections (defined as infections causing fevers and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours), active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, history of ventricular tachycardia or ventricular fibrillation, active cardiac arrhythmias (active atrial fibrillation is not allowed, resolved atrial fibrillation not requiring current treatment is allowed (anticoagulants count as current treatment) ), active obstructive or restrictive pulmonary disease, active autoimmune diseases such as rheumatoid arthritis Hospitalization within the 7 days prior to enrollment Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) | 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, Diffuse Large B Cell Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Leukemia Marginal Zone Lymphoma Men and women ≥ 18 years of age. 2. Patients must have histologic confirmation of relapsed or refractory lymphoma. 3. Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites. a) CT scan showing at least i. 2 or more clearly demarcated lesions/nodes with a long axis >1.5cm and short axis ≥ 1.0cm, or ii. 1 clearly demarcated lesion/node with a long axis >2.0cm and short axis ≥1.0cm. 4. Patient must have been previously treated for B cell non-Hodgkin lymphoma with any of the allowable below: 1. First-line treatment with rituximab and an anthracycline-based chemotherapy. 2. Monotherapy rituximab, dosed prior to first-line rituximab combined with anthracycline containing chemotherapy, or as maintenance therapy. 3. Radiotherapy as part of the first-line treatment plan including anthracycline and rituximab. 5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 6. Life expectancy of greater than 6 weeks. 7. Patients must have normal organ and marrow function as defined below, 1. absolute neutrophil count ≥ 1000/microliters (mcL) (unless due to lymphoma involvement of the bone marrow), 2. platelets ≥75,000/mcL (unless due to lymphoma involvement of the bone marrow), 3. total bilirubin <1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert's disease), 4. Aspartate transaminase (AST) (SGOT)/Alanine transaminase (ALT) (SGPT) ≤ 2.5 × institutional upper limit of normal (unless due to lymphoma involvement of liver), 5. creatinine within normal institutional limits, or 6. creatinine clearance ≥40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. (unless due to lymphoma). 8. Major surgical procedure within 28 days of first dose of study drug. If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug. 9. Women who are sexually active and can bear children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib + R-ICE. 10. Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib + R-ICE. 11. Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of study drug. 12. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. 13. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations) Germinal-center cell-of-origin DLBCL. 2. Patients who have had chemotherapy or radiotherapy < 21 days prior to first administration of study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 3. Patients who are receiving any other investigational agents. 4. Patients with known central nervous system involvement of lymphoma. 5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to acalabrutinib or R-ICE with the exception of first-infusion reaction to rituximab. 6. 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. Recent infections requiring systemic treatment need to have completed therapy > 7 days before the first dose of study drug. 7. Pregnant women are excluded from this study because an acalabrutinib R-ICE is a chemotherapy program with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with acalabrutinib R-ICE, breastfeeding should be discontinued if the mother is treated with acalabrutinib R-ICE. 8. HIV-positive patients on combination antiretroviral therapy are eligible, unless the patient's CD4 count is below the institutional lower limit of normal, or the patient is taking prohibited CYP3A4/5 strong inhibitors or inducers. 9. Patients may not have received any anti-cancer therapy for their primary rel/ref DLBCL with the exception of palliative radiation therapy (RT). 10. Uncontrolled Autoimmune Hemolytic Anemia or immune thrombocytopenia purpura (ITP) resulting in (or as evidenced by) declining platelet or Hgb levels within the 4 weeks prior to first dose of study drug. 11. Presence of transfusion-dependent thrombocytopenia. 12. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor. 13. History of prior malignancy, with the exception of the following: 1. Malignancy treated with curative intent felt to be at low risk for recurrence by treating physician, 2. Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease, 3. Adequately treated cervical carcinoma in situ without current evidence of disease. 14. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to first dose with study drug. 15. Unable to swallow capsules, or disease significantly affecting gastrointestinal function or, resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction. 16. Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) Hepatitis C antibody positive patients are eligible if PCR is negative. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis. 17. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 18. Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study at risk. 19. Received anticoagulation therapy with Coumadin or equivalent vitamin K antagonists within the last 28 days. 20. Vaccinated with live, attenuated vaccines with 4 weeks of first does of study drug. 21. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology for Adverse Event (CTCAE, version 5), grade ≤1, or to the levels dictated in the inclusion/ with the exception of alopecia. 22. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia. 23. Unwilling or unable to participate in all required study evaluations and procedures. 24. Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the NCI/Child Pugh classification. 25. Breastfeeding or pregnant. 26. Concurrent participation in another therapeutic clinical trial. 27. Patients who require proton pump inhibitors at baseline (prior to fist dose of study drug) or strong CYP3A4 inhibitor or inducer and are not able to switch to another medication | 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, Myeloid Neoplasm Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Initial presentation with > 10% myeloid blasts in peripheral blood or marrow and, after at least one course of induction treatment, now with > 5% blasts in peripheral blood or marrow, as assessed by morphology or multiparameter flow cytometry (MFC). Outside diagnostic material is acceptable if reviewed here. Patients may never have achieved an initial complete remission (< 5% blasts in marrow, absolute neutrophil count > 1,000 per microliter, platelet count > 100,000 per microliter) or may have relapsed from such a remission. Note that although "AML" is formally denoted by > 20% blasts and other high-grade myeloid neoplasm by 10-20% blasts, these two entities often have similar prognoses and respond similarly to therapy, with trials at University of Washington (UW)/Seattle Cancer Care Alliance (SCCA) as well as MD Anderson and various European cooperative groups not distinguishing between AML and other high grade myeloid neoplasms Treatment related mortality (TRM) score < 13.1 Bilirubin < 2.0 mg/dl unless abnormalities thought due to organ infiltration by AML as suggested for example by white blood cell (WBC) > 25,000 and rising rapidly Creatinine < 2.0 mg/dl unless abnormalities thought due to organ infiltration by AML as suggested for example by WBC > 25,000 and rising rapidly Left ventricular ejection fraction > 45% by multigated acquisition scan (MUGA) scan or echocardiography, performed within 6 months prior to consent Off any active therapy for AML other than hydroxyurea for at least 1 week prior to study registration unless patient has rapidly progressive disease with resolution of all grade 2-4 non-hematologic toxicities. Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000 and in whom there is a delay in scheduling a MUGA scan or other logistical delays can receive two doses of cytarabine (500 mg/m^2 each, but dosing is ultimately based on physician discretion) Men and women of childbearing potential must agree to use adequate contraception Not pregnant or lactating Not receiving other investigational agents Provision of informed written consent on study-specific consent form | 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, Leukemia, Lymphocytic, Chronic, B-Cell Patients with diagnosis of B-cell CLL 2. Disease status defined as refractory to or relapsed after at least one prior therapy. 3. Presence of measurable lymphadenopathy presence of > 1 nodal lesion 4. ECOG performance status ≤ 2. 5. Adequate bone marrow, liver, and renal function Richter's (large cell) transformation, or PLL transformation. 2. Cancer therapy/ any cancer investigational drug within 3 weeks (21 days) or 5 half-lives (whichever is shorter). 3. Prior exposure to drug that inhibits PI3K 4. Patient with ASCT/Allo-SCT receiving treatment for active GVHD. 5. Ongoing severe systemic bacterial, fungal or viral infection. 6. Central nervous system (CNS) involvement of leukemia or lymphoma. 7. Ongoing immunosuppressive therapy including systemic corticosteroids. 8. Known history of severe liver injury as judge by investigator. 9. Any severe and/or uncontrolled medical conditions or other conditions that could affect patient participation 10. Women who are pregnant or lactating. 11. Known seropositive requiring anti-viral therapy for i. human immunodeficiency virus (HIV) infection. ii. hepatitis B virus (HBV) infection iii. hepatitis c virus (HCV) infection iv. active CMV infection - | 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, Small Lymphocytic Leukemia (SLL) Chronic Lymphocytic Leukemia (CLL) Age greater than or equal to 18 years Diagnosis of CLL or SLL as defined by the following CLL: clonal B cells greater than or equal to 5,000 cells/uL in the peripheral blood SLL: lymphadenopathy with histopathological evaluation consistent with SLL, absence of cytopenia caused by clonal marrow infiltrate, and <5,000 B cells/uL in the peripheral blood Immunophenotype: co-expression of CD5, CD19, CD20, and CD23. CD23 negative cases may be included if there is an absence of t(11;14) Current treatment with ibrutinib for CLL Mutations in BTK and/or PLCG2 (from a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory) with measurable disease characterized by at least 1 of the following Lymphadenopathy: greater than or equal to 1 lymph node measuring greater than or equal to 1.5 cm in the greatest diameter Splenomegaly: spleen measuring > 13 cm in craniocaudal length Lymphocytosis: greater than or equal to 5,000 B cells/ L Richter transformation of CLL into an aggressive lymphoma History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function Prior history of drug-induced colitis or pneumonitis Known hypersensitivity to any of the study drugs Major surgery within 4 weeks prior to screening Central nervous system (CNS) non-Hodgkin lymphoma (NHL); lumbar puncture not required unless CNS involvement is clinically suspected Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects with detectable viral load) Infection with hepatitis B or hepatitis C Subjects with a positive hepatitis B surface antigen (HBsAg)) will be excluded Subjects with or hepatitis C antibody (HCV Ab) will be excluded, unless they have received curative treatment for hepatitis C virus (HCV) and have undetectable viral RNA by PCR | 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): 18.0-85.0, CLL/SLL ≥18 years of age. 2. Histologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) according to the 2018 international workshop (IW) CLL who must have relapsed or be refractory to at least one prior therapy for CLL/SLL and require treatment by 2018 IWCLL criteria. 3. ECOG) ≤2. 4. Patient must have objectively documented evidence of disease progression prior to study entry such as: escalating lymphocytes count with an increase > 50% over a period of two months or doubling time in less than 6 months; enlarging adenopathy or splenomegaly; increasing cytopenias; clinical B symptoms -night sweats, fatigue, > 1% weight loss in 6 months, fevers > 100.50F for ≥ one month without infection. 5. In Part 1 of the APG-2575 monotherapy dose escalation portion, patients eligible for dose expansion at doses lower than MTD will have received ≤ 3 prior systemic lines of therapy. 6. Adequate bone marrow function independent of growth factor: 1. Absolute neutrophil count (ANC)≥1.0× 109/L in patient without bone marrow involvement. This criterion does not apply to patients with bone marrow involvement by CLL/SLL. 2. Platelets count ≥30 x 109/L (entry platelet count must be independent of transfusion within 7 days of first dose of study drug). 7. Adequate renal and hepatic function as indicated by: a. Serum creatinine ≤1.5×upper limit of normal (ULN); if serum creatinine is >1.5×ULN, creatinine clearance must be ≥ 50 mL/min, calculated using the Cockcroft and Gault formula(140-Age)x mas (kg)/(72x creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976) b. Total bilirubin ≤1.5 x ULN, except patients with known Gilbert's syndrome. c. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2.5 x ULN, Alkaline phosphatase<2.5×ULN d. International normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT)≤1.5×ULN unless the patient is receiving anticoagulant therapy as long as PT or APTT is within therapeutic range of intended use of anticoagulants. 8. Females of childbearing potential (i.e. not postmenopausal for at least 2 years or surgically sterile) must have negative results for pregnancy test performed: a. At Screening on a serum sample obtained within 14 days prior to the first study drug administration b. Prior to dosing on a urine sample obtained on the first day of study drug administration, if it has been>7 days since obtaining the serum pregnancy test results. 9. Females of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: 1. Total abstinence from sexual intercourse as the preferred lifestyle of the patient; periodic abstinence is not acceptable; 2. Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy; 3. Intrauterine device (IUD); 4. Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal fellies or cream AND a condom); 5. Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to study drug administration. If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to study drug administration. 10. Male patients must refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug. 11. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures). 12. Willingness and ability to comply with study procedures and follow-up examination Patient has undergone allogeneic stem cell transplant < 90 days 2. Patient has active graft-versus-host disease or require immunosuppressive therapy. 3. Richter's Syndrome. 4. Prior anti-Bcl-2 treatment (except patients who discontinued treatment for reasons other than disease progression) 5. For combination cohorts: 1. In the acalabrutinib and APG-2575 cohort, patients who are on anticoagulants or patients that discontinued due to acalabrutinib toxicity (Note: Patients who received a BTK inhibitor therapy may participate whether, or not, they progressed following BTK inhibitor treatment). 2. Prior CDK-9 inhibitor in the voruciclib plus APG-2575 cohort 6. Known human immunodeficiency virus syndrome (HIV) infection 7. Known active hepatitis B infection, as defined seropositivity for Hep B surface antigen (HBsAg) or known hepatitis C infection as determined by hepatitis C antibody with elevated liver enzymes as defined in the or any other evidence of active hepatitis C such as currently on treatment 8. Has known central nervous system (CNS) involvement. 9. Prior malignancy that required treatment and has shown recurrence within 2 years of screening (except for non-melanoma skin cancer or adequately treated carcinoma in situ of cervix or breast). Cancer treated within 2 years with curative intent and without recurrence as well as prostate cancer on active surveillance are allowed. 10. Concurrent treatment with an investigational agent, received biologics (≤28 days), or small molecule targeted therapies (≤5 half-life) or other anti-cancer therapies (including chemotherapy) ≤14 days of first dose of study drug 11. Patient is pregnant or breast feeding 12. Has received the following within 7 days prior to the first dose of study drug: 1. Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for anti-neoplastic intent; 2. CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin; 3. Potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort; 13. Radiation within 14 days of study entry 14. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ grade 1 or baseline, except alopecia or neuropathy. 15. Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patient with active wound healing, patients who have had major surgery within 28 days from 1st dose of study drug 16. Has a cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain. 17. Unstable angina or myocardial infarction within 3 months of enrollment 18. QTc interval> 480ms (Bazett or Fredericia formulae) or other remarkable abnormal ECG findings, including second-degree type II atrioventricular block, third-degree atrioventricular block or bradycardia (ventricular rate of less than 50 beats per minute). 19. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the opinion of the Investigator. 20. Uncontrolled concurrent illness including, but not limited to: uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements. 21. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the 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): 18.0-70.0, Helminthiasis Helminth Infection The included volunteer is a researcher within parasitology with focus on Trichuris trichiura and Trichiura suis. He planned to infect himself under medical supervision. This was his third self-infection with Trichuris. The only clinical criterion for his in the study was that he was healthy N/A | 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, Irritable Bowel Syndrome Patients who fulfil Rome IV for the diagnosis of IBS. 2. Patients were investigated to other gastrointestinal organic cause(s). 3. Moderate-to-severe IBS symptoms, as indicated by a score of ≥175 on the IBS Severity Scoring System (IBS-SSS) Pregnant or lactating women. 2. The use of antibiotics or probiotics within 1 month prior to FMT. 3. Immunocompromised patients defined as those treated by immune suppressive medications. 4. Patients with co-morbidity such as kidney failure or chronic heart disease. 5. System disease such as diabetes. 6. Patients with serious psychiatric disorders or drug abuse | 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, Thoracic Surgery All consecutive patients admitted for lobectomy or wedge video-assisted thoracoscopy Opioid Free Anesthesia (OFA) administration was left to the discretion of the attending anesthetist according to his or her practices and habits age 18 or over lobectomy or wedge resection by Video-Assisted Thoracoscopy Surgery (VATS) toxicomania epidural analgesia use thoracotomy conversion Patient-Controlled Analgesia with morphine (PCA) Patient who object to take part of 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, Nonsmall Cell Lung Cancer Performance Status Patients must have histologically confirmed NSCLC that is metastatic or unresectable for which standard curative measures do not exist No prior systemic treatment with either chemotherapy or immunotherapy for non-curative intent. Patients may have previously received cancer treatment with curative intent for prior early stage disease At least 18 years old ECOG performance status of 0-2, as determined by the treating physician in the consult note Life expectancy of greater than 3 months Patients must have radiographically measurable metastatic disease by criteria Patients must have normal organ and marrow function as defined below absolute neutrophil count ≥1,000/mcL platelets ≥100,000/mcL Chemotherapy agents are known to be teratogenic, therefore women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Nonsmall cell lung cancer that is known at registration to be positive for a tumor activating alteration for which first line targeted therapy is indicated; specifically, a targetable mutation in epidermal growth factor receptor (EGFR), gene rearrangement of anaplastic lymphoma kinase (ALK), gene rearrangement of c-ros oncogene 1 (ROS1), or mutation in B isoform of rapidly accelerated fibrosarcoma (B-Raf) Known to have an active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, systemic corticosteroids, or immunosuppressive drugs) History of (non-infectious) pneumonitis that required systemic corticosteroids 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 Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects with chemotherapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued | 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 Transformation Confirmed diagnosis of CLL according to iwCLL (Hallek et al, 2018) 2. Confirmed histopathological diagnosis of RT 3. Creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection 4. Adequate liver function as indicated by a total bilirubin ≤ 2x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL/RT or to Gilbert's Syndrome, in which case a max. total bilirubin ≤ 4 x and AST/ALT ≤ 5 x the institutional ULN value are required 5. 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 two months until 2 months after last dose of zanubrutinib), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration 6. Age at least 18 years 7. ECOG performance status 0-2, ECOG 3 is only permitted if related to CLL or RT (e.g. due to anaemia or severe constitutional symptoms) 8. Life expectancy ≥ 6 months 9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements Patients who did not respond to previous line of RT therapy (i.e. primary progressive patients) 2. Patients with more than one prior line of RT therapy 3. Allogenic stem cell transplantation within the last 100 days or signs of active graft-versus-host disease (GVHD) after prior allogeneic stem cell transplantation within any time 4. Patients with confirmed progressive multifocal leukoencephalopathy (PML) 5. Uncontrolled autoimmune condition 6. Malignancies other than CLL currently requiring systemic therapies 7. Active infection currently requiring systemic treatment 8. Any comorbidity or organ system impairment rated with a Cumulative Illness Rating Scale (CIRS) score of 4, excluding the eyes/ears/nose/throat/larynx organ system, or any other life-threatening illness, medical condition or organ system dysfunction that in the investigator´s opinion could comprise the patients safety or interfere with the absorption or metabolism of the study drugs 9. Requirement of therapy with strong CYP3A4 inhibitors/inducers 10. Requirement of therapy with phenprocoumon or other vitamin K antagonists. 11. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration 12. Known hypersensitivity to tislelizumab, zanubrutinib or any of the excipients 13. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 14. Fertile men or women of childbearing potential unless surgically sterile or ≥ 2 years after the onset of menopause, or willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 12 months after the end of study treatment. 15. Vaccination with a live vaccine <28 days prior to randomization 16. Legal incapacity 17. Prisoners or subjects who are institutionalized by regulatory or court order 18. 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, Lymphocyte Depletion Willingness and ability to provide written informed consent and to comply with the study protocol. 2. Diagnosis of biopsy confirmed non-small cell lung cancer (NSCLC) with planned treatment with SBRT as definitive therapy OR imaging confirmed lung lesion for which SBRT is planned for primary lung cancer (when clinician determines biopsy is not indicated), Registration should occur within 5 business days (before or after) of planning CT. 3. Patients must decline surgery or tumor(s) must be considered to be medically inoperable 4. Location and size of tumor Participants must have either peripherally located tumors (> 2 cm in all directions from the proximal bronchial tree; see Figure 2 above) as defined by RTOG 0915, OR centrally located tumors (tumor size ≤ 5 cm, tumors within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura) as defined by RTOG 0813. 5. Patients with recurrence of prior surgically treated lung cancers are eligible if no further surgery is planned and they otherwise meet the criteria. 6. Measurable disease on chest CT, PET CT, CT simulation at diagnosis ( must be within 8 weeks of SBRT). 7. Pre radiation therapy total lymphocyte count > 0.5k/μL on blood count drawn within 2 weeks prior to registration. 8. In the opinion of the treating clinician, patient is medically able to tolerate the study SBRT treatment of 50-60 Gy in 5 fractions. 9. ECOG performance status of 0-2. 10. Age ≥ 18 years. 11. If participant is a woman of childbearing potential (WOCBP), agreement to adhere to contraception requirements from the time of consent through completion of SBRT Prior history of radiation therapy for any reason. 2. Systemic anti-cancer therapy within the last year prior to registration or planned use during or within 6 months following SBRT. 3. Major surgery within the last 30 days before registration. 4. Subject is a prisoner. 5. Subject is a pregnant woman. 6. Patient is not medically able to tolerate the study SBRT treatment of 50-60 Gy | 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, COVID-19 COVID-19 Immunisation A subject must meet all of the following to be eligible to participate in this study: 1. Provides written informed consent prior to initiation of any study procedures. 2. Be able to understand and agrees to comply with planned study procedures and be available for all study visits. 3. Agrees to the collection of venous blood per protocol. 4. Male or non-pregnant female, >/= to 18 years of age at time of enrollment. 5. Body Mass Index (BMI) 18.0-35.0 kg/m^2, inclusive (< 56 years of age), at screening; BMI 18.0-30.0 kg/m^2, inclusive (>/= 56 years of age), at screening. 6. Women of childbearing potential* must agree to use or have practiced true abstinence** or use at least one acceptable primary form of contraception.***, **** Note: These are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the do not apply to subjects in a same sex relationship) Not of childbearing potential post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement) True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) Acceptable forms of primary contraception monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products Must use at least one acceptable primary form of contraception for at least 30 days prior to the first vaccination and at least one acceptable primary form of contraception for 60 days after the last vaccination. 7. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each vaccination. 8. Male subjects of childbearing potential*: use of condoms to ensure effective contraception with a female partner of childbearing potential from first vaccination until 60 days after the last vaccination. *Biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy. 9. Male subjects agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination. 10. In good health.* *As determined by medical history and physical examination to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of safety of subjects. Chronic medical diagnoses/conditions should be stable for the last 60 days (no hospitalizations, emergency room (ER), or urgent care for condition or need for supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis/condition in the 60 days before enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the participating site principal investigator (PI) or appropriate sub-investigator, will not be considered a deviation of this criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the subject or interference with the evaluation of responses to study vaccination. 11. Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius). 12. Pulse no greater than 100 beats per minute. 13. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive. 14. Clinical screening laboratory evaluations (white blood cell (WBC), hemoglobin (Hgb), platelets (PLTs), alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), alkaline phosphatase (ALP), total bilirubin (T. Bili), Lipase, prothrombin time (PT), and partial thromboplastin time (PTT)) are within acceptable normal reference ranges at the clinical laboratory being used. 15. Must agree to have samples stored for secondary research. 16. Agrees to adhere to Lifestyle Considerations throughout study duration. 17. Must agree to refrain from donating blood or plasma during the study (outside of this study). Leukapheresis A subject must meet all of the following to be eligible for leukapheresis: 1. Written informed consent for leukapheresis is provided. 2. Weight >/= 110 pounds. 3. Screening laboratory evaluations are within acceptable ranges at the site where the leukapheresis procedure will be performed. 4. Negative urine or serum pregnancy test within 48 hours of the leukapheresis procedure for women of childbearing potential. 5. Adequate bilateral antecubital venous access. 6. No use of blood thinners, aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) at least 5 days before the leukapheresis procedure. 7. Enrolled in cohorts 2, 3, 5, 10, or 11, and possibly cohort 6, if enrolled, and completed the two-dose vaccination series. Optional Substudy 1. Enrolled in the main study and received both the first and second mRNA-1273 vaccinations. 2. Provides written informed consent for the third mRNA-1273 vaccination. 3. Agrees to the collection of venous blood per substudy. 4. Must agree to have samples stored for secondary research. 5. Women of childbearing potential have had a negative urine pregnancy test within 24 hours before the third mRNA-1273 vaccination. 6. Women of childbearing potential* must agree to use or have practiced true abstinence** or use at least one acceptable primary form of contraception.***/**** Not of childbearing potential post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure® placement) True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) Acceptable forms of primary contraception monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products. ****Must use at least one acceptable primary form of contraception for at least 30 days prior to the third mRNA-1273 vaccination and for at least 30 days after the third mRNA-1273 vaccination A subject who meets any of the following will be excluded from participation in this study: 1. Positive pregnancy test either at screening or just prior to each vaccine administration. 2. Female subject who is breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last vaccination. 3. Has any medical disease or condition that, in the opinion of the participating site principal investigator (PI) or appropriate sub-investigator, precludes study participation.* *Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. 4. Presence of self-reported or medically documented significant medical or psychiatric condition(s).* *Significant medical or psychiatric conditions but are not limited to: Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics. Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), history of myocarditis or pericarditis as an adult, myocardial infarction (MI) within past 6 months, coronary artery bypass surgery or stent placement, or uncontrolled cardiac arrhythmia. Neurological or neurodevelopmental conditions (e.g., history of migraines in the past 5 years, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease). Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed. An autoimmune disease, including hypothyroidism without a defined non-autoimmune cause, localized or history of psoriasis. An immunodeficiency of any cause. Chronic kidney disease, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2. 5. Has an acute illness*, as determined by the participating site PI or appropriate sub-investigator, with or without fever [oral temperature >/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)] within 72 hours prior to each vaccination. *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol. 6. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening. 7. Has participated in another investigational study involving any investigational product* within 60 days, or 5 half-lives, whichever is longer, before the first vaccine administration. *study drug, biologic or device 8. Currently enrolled in or plans to participate in another clinical trial with an investigational agent* that will be received during the study-reporting period.** *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. **13 months after the first vaccination. 9. Has previously participated in an investigational study involving lipid nanoparticles (LNPs) (a component of the investigational vaccine assessed in this trial). 10. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines. 11. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness.* *Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period prior to vaccine administration (Day 1). The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted. 12. Anticipating the need for immunosuppressive treatment within the next 6 months. 13. Received immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study. 14. Has any blood dyscrasias or significant disorder of coagulation. 15. Has any chronic liver disease, including fatty liver. 16. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 6 months before the first vaccine administration. 17. Has a positive test result for drugs of abuse at screening or before the first vaccine administration. If cannabis is the only detected drug, is permitted. 18. Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site (deltoid region). 19. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination. 20. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination. 21. Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to or during the study. 22. Close contact of anyone known to have SARS-CoV-2 infection within 30 days prior to vaccine administration. 23. History of COVID-19 diagnosis. 24. On current treatment with investigational agents for prophylaxis of COVID-19. 25. Current use of any prescription or over-the-counter medications within 7 days prior to vaccination, unless approved by the investigator or necessary to manage a chronic condition. 26. Plan to travel outside the United States (US) (continental US, Hawaii, and Alaska) from enrollment through 28 days after the last vaccination. 27. Reside in a nursing home or other skilled nursing facility or have a requirement for skilled nursing care. 28. Non-ambulatory. 29. For subjects >/= 56 years of age, history of chronic smoking within the prior year. 30. For subjects >/= 56 years of age, current smoking or vaping. 31. For subjects >/= 56 years of age, individuals currently working with high risk of exposure to SARS-CoV-2 (e.g., active health care workers with direct patient contact, emergency response personnel). Optional Substudy Anaphylaxis or other systemic hypersensitivity reaction following a mRNA-1273 or any other vaccination. 2. Immediate allergic reaction of any severity after mRNA-1273 or any of its components.* *Including polyethylene glycol (PEG) 3. Immediate allergic reaction of any severity to polysorbate.* *Due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG 4. History of an SAE judged related to mRNA-1273 vaccine. 5. Female subject who is breastfeeding or plans to breastfeed from the time of the third mRNA-1273 vaccination through 30 days after the third mRNA-1273 vaccination. 6. Has an acute illness*, as determined by the participating site PI or appropriate sub-investigator, with or without fever [oral temperature >/=38.0°C (100.4°F)], within 72 hours prior to the third mRNA-1273 vaccination. *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the substudy. 7. Has received any approved, authorized or investigational COVID-19 vaccine outside of this trial. 8. Any clinically significant medical condition that, in the opinion of the investigator, poses an additional risk to the subject from vaccination. 9. History of documented COVID-19 infection. 10. Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes substudy participation. 11. Received or plans to receive a licensed vaccine, other than a COVID-19 vaccine, within 2 weeks before or after the third mRNA-1273 vaccination | 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): 0.0-22.0, Acute Myeloid Leukemia All patients must be enrolled on APEC14B1 and consented to Screening (Part A) prior to enrollment and treatment on AAML1831. Submission of diagnostic specimens must be done according to the Manual of Procedures). Risk stratification will not be possible without the submission of viable samples. Given there are multiple required samples, bone marrow acquisition techniques such as frequent repositioning or performing bilateral bone marrow testing should be considered to avoid insufficient material for required studies. Consider a repeat marrow prior to starting treatment if there is insufficient diagnostic material for the required studies Patients must be less than 22 years of age at the time of study enrollment Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease Patient must have 1 of the following >= 20% bone marrow blasts (obtained within 14 days prior to enrollment) In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy < 20% bone marrow blasts with one or more of the genetic abnormalities (sample obtained within 14 days prior to enrollment) A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment) ARM C: Patient must be >= 2 years of age at the time of Late Callback ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology Patients with myeloid neoplasms with germline predisposition are not eligible Fanconi anemia Shwachman Diamond syndrome Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Any other known bone marrow failure syndrome Any concurrent malignancy Juvenile myelomonocytic leukemia (JMML) Philadelphia chromosome positive AML Mixed phenotype acute leukemia Acute promyelocytic leukemia | 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 Mediastinal Lymphadenopathy Thoracic Cancer Patient age greater to or equal than 18 years old Receiving an endobronchial ultrasound for any diagnostic reason Patients under 18 years old Patient refuses consent to undergo endobronchial ultrasound or is incapable of decision making | 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, Anxiety Digital Eye Strain Grade 7 (12-13 years old) students in Duanzhou District, Zhaoqing city Students under home confinement and enrolled in online learning courses, during the COVID-19 outbreak Autism Spectrum Disorders and Pervasive Developmental Delay or Disorder Mental Retardation Psychotic Disorders and Schizophrenia Mania or Hypomania disorders Suicidal behavior and/or acute plan that require higher level of care Participation in psychotherapy | 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, Covid-19 Mental Health Disorder Stress Disorder Anxiety Depression SARS-CoV-2 Legal age Currently working on a health service that provides care to COVID-19 patients Give informed consent Inability to use electronic devices (required to complete the survey) | 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, Low Back Pain Patients reported persistent LBP of more than 3/10 in the last 12 weeks Subjects with acute low back pain, "red flags" indicating signs of serious pathology, previous back surgery, pregnancy, specific rheumatological diseases, spodylolysis or spondylolisthesis, spinal tumor or spinal fracture, mental disorders, or neurological diseases will be 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): 18.0-70.0, COVID-19 Adult SARI patients with 2019-ncov infection confirmed by PCR; Absolute value of lymphocytes < 0. 6x 109/L; Severe respiratory failure within 48 hours and requires admission to ICU. (severe respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive pressure mechanical ventilation (including non-invasive and invasive mechanical ventilation, PEEP>=5cmH2O)) Age < 18 Pregnant Allergic to experimental drugs and patients have the following conditions: 1. Hypercholesterolemia 2. Hypertriglyceridemia 3. Liver disease 4. Renal disease 5. Sjögren syndrome 6. Pregnancy 7. Lactation 8. Depressive disorder 9. Body mass index less than 18 points or higher than 25 points 10. Contraindications for hormonal contraception or intrauterine device. 11. Autoimmune diseases A history of organ, bone marrow or hematopoietic stem cell transplantation 12. Patients receiving anti-hcv treatment 13. Permanent blindness in one eye 14. History of iritis, endophthalmitis, scleral inflammation or retinitis 15-90 days of retinal detachment or eye surgery 15. The competent physician considered it inappropriate to participate in the study 16. HIV infection or other immunodeficiency or with an absolute neutrophil count ≤1.0 × 109/L 17. Abnormal liver biochemistry (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase) >1.5 × upper limit of normal or total bilirubin > upper limit of normal (unless Gilbert's disease with normal conjugated bilirubin) 18. Any of the following laboratory abnormalities are present at baseline Platelet count <150×109/L Serum albumin ≤ 3.5 g/dL INR ≥1.2 CPK ≥ ULN. 19. Significant liver fibrosis as evidenced by Fibrosis-4 (FIB-4) score >3.25 20. History of hypersensitivity to retinoic acid or any of its excipients or the class of neutrophil elastase inhibitors Known hypersensitivity to medications used in the study procedures (e.g. midazolam, fentanyl, and lidocaine for bronchoscopy) | 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, T-LGL Leukemia Clpd-Nk The gender of the patient is not limited, and the age is ≥18 years old; 2. Must meet diagnostic of T-LGLL or CLPD-NK according to WHO 2016 version; 3. The patient is treatment naive or received single methotrexate less than 4 weeks and without response. If relapsed or refractory patients, the patients must be naive for both thalidomide and methotrexate. 4. With LGLL treatment indications, it mainly includes (meets at least one of the following conditions): 1. ANC <0.5 × 10^9 / L 2. HGB <100g / L or need red blood cell infusion to maintain 3. PLT <50 × 10^9 / L 4. Combining autoimmune diseases that require treatment 5. symptomatic splenomegaly 6. Severe B symptoms 7. Pulmonary hypertension. 5. ECOG performance status score is 0-2; 6. The patient's expected survival time is ≥ 6 months Unable to understand or follow the research procedure; 2. Co-occurrent malignant tumors that has to be treated or course the symptom; 3. Other serious diseases, such as liver, kidney, heart, lung, nerve or metabolic diseases, may impede the ability of patients to tolerate methotrexate, cyclophosphamide or cyclosporin A; 4. ALAT / ASAT or alkaline phosphatase> 3 times the normal value; 5. Creatinine clearance <60ml / min; 6. Serological evidence of active infection of HIV, hepatitis C or hepatitis B; 7. Ineffective contraception; 8. Positive pregnancy test; 9. Pregnant women | 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, Cardiopulmonary Bypass Cardiac Surgery Patient weight ≤60kg Age ≥18 years old The patient underwent cardiac arrest surgery Heart transplant patients Emergency cardiac surgery patients Patients who had been assisted by extracorporeal membrane oxygenator (ECMO) or assisted by left heart before operation Left ventricular ejection fraction (LVEF) < 30% Patients with coagulation dysfunction before surgery Patients with preoperative hepatic and renal insufficiency Recent cerebrovascular accident 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, Severe COVID-19 Disease Male or female participants ≥ 18 years of age. 2. Participants with SARS-CoV-2 infection, as defined by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent test. 3. Must have pulmonary infiltrate on radiologic examination. 4. Participant must have a clinical diagnosis of high-risk ARDS (as defined by a PaO2-to-FiO2 ratio of < 150 mm Hg) requiring intensive respiratory support, including non-invasive methods such as high-flow nasal cannula or mechanical ventilation. 5. AST and ALT ≤ 3 x upper limit of normal (ULN). 6. Consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn at any time without prejudice to future medical care. Informed consent can be obtained from healthcare proxy if the participant is unable to provide consent due to medical status Active uncontrolled infection with a non-COVID-19 agent. 2. Diagnosis of ARDS that is not considered to be high-risk, as defined by PaO2-to-FiO2 ratio of ≥ 150 mm Hg. 3. Any irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%. 4. End-stage liver disease with ascites unrelated to COVID-19 (Childs Pugh score > 12). 5. Uncontrolled or significant cardiovascular disease, including but not limited to: (a) myocardial infarction, stroke, or transient ischemic attack within the past 30 days; (b) uncontrolled angina within the past 30 days; (c) any history of clinically significant arrhythmias such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes; and (d) history of other clinically significant or uncontrolled heart disease, including: cardiomyopathy, congestive heart failure with New York Heart Association functional classification III or IV, myocarditis, pericarditis, or significant pericardial effusion. 6. Known chronic kidney disease of Stage 4 or 5 severity or requiring hemodialysis. 7. COVID-19-associated acute kidney injury requiring dialysis. 8. HIV, hepatitis B, or hepatitis C seropositive. 9. Patients with baseline QTc interval prolongation, as defined by repeated demonstration of a QTc interval >500 milliseconds. 10. Patients on hydroxychloroquine (must discontinue at least 2-days before study entry). 11. Pregnant or breastfeeding participants. 12. Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception. Effective forms of birth control, which must be continued through the entire on-study 6-month interval, Abstinence; Intrauterine device (IUD); Hormonal (birth control pills, injections, or implants); Tubal ligation; or Vasectomy. 13. Participants with malignancy requiring active therapy (not including non-melanoma skin cancer). 14. Recipients of allogeneic hematopoietic cell transplant or solid organ transplant. 15. History of WHO Class III or IV pulmonary hypertension. 16. Severe thromboembolic disease, as defined by: administration of thrombolytic agents, insertion of vena cava filter, or pulmonary thrombectomy within one-week interval prior to screening. 17. Participants may be excluded at the discretion of the PI or if it is deemed that allowing participation would represent an unacceptable medical or psychiatric risk | 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, Lymph Node Disease Ultrasound Therapy; Complications Patients with one of these four diseases Patients with severe heart and brain diseases and poor coagulation function. 2. Undiagnosed patients are not included in the statistical analysis. 3. Image distortion of CEUS acquisition cannot be analyzed | 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, Persistent Atrial Fibrillation Longstanding Persistent Atrial Fibrillation Diagnosed persistent and/or long-term Failed medical therapy with antiarrhythmic drug therapy Expected life expectancy of less than one year Previous heart operation Previous ablation procedure Left ventricular ejection fraction below 30 % Severe valvular heart disease Acute coronary syndrome Diminished functional capacity due to non-cardiac co-morbidities 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, Metastatic Gastric Cancer Locally Advanced Gastric Adenocarcinoma Written informed consent obtained Age ≥ 18 years at time of study entry, no gender limit Participants must have histologically or cytologically confirmed adenocarcinoma of the stomach (including adenocarcinoma of the gastroesophageal junction) At least one measurable site of disease as defined by with spiral CT scan or MRI CT or MRI showed unresectable locally advanced gastric cancer (imaging stage T4b and / or second station lymph node > 3cm or fusion mass) or limited metastatic gastric cancer with any of the following single site metastasis: 1. Retro-peritoneal lymph node metastasis (RPLM) (e.g. para-aortic, intra-aorto-caval, para-pancreatic or mesenteric lymph nodes). 2. Single or bilateral Krukenberg tumors. 3. No more than 5 liver metastases, and the maximum diameter of the lesions was less than 5 cm. 4. Adrenal metastasis. 5. Localized potentially operable peritoneal carcinomatosis: stage P1 according to classification of the"Japanese Research Society for Gastric Cancer (JRSCGC)" No clinically visible peritoneal metastasis (such as CT imaging confirmation or ascites) No prior anti-tumor therapy Performance status (PS) < 2 (ECOG scale) Life expectancy of at least 12 weeks Adequate blood count, liver-enzymes, and renal function: hemoglobin≥90g/dL,absolute neutrophil count ≥ 1.5×109/L, platelets ≥100 x109/L; Total bilirubin < 1.5x upper normal limit (UNL), Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) <2.5 x ULN, if liver metastasis existed, SGOT,SGPT<2.5xULN. International normalized ratio (INR) ≤2.5 x ULN, Serum Creatinine ≤ 1 x institutional ULN or creatinine clearance (CrCl) >50ml/min (if using the Cockcroft-Gault formula ) A history of other malignancies within 3 years prior to enrollment, except for cervical carcinoma in situ or skin basal cell carcinoma that had been cured Accompanied with brain or meningeal metastasis Malignant pleural and peritoneal effusion Accompanied by gastrointestinal obstruction, gastrointestinal bleeding (fecal occult blood +++ )or perforation Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137,or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) Has an active or history of autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or with high risk (such as receiving immunosuppressive therapy after organ transplantation), but in the past two years with vitiligo, psoriasis, alopecia or Graves' disease without systemic treatment, hypothyroidism with thyroid hormone replacement therapy only and type I diabetes only need insulin replacement therapy can be enrolled Suffering from interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung disease and radiation pneumonia Participate in other clinical studies of drugs (subject to the use of trial drugs) within 4 weeks before the first administration, unless participating in observational (non intervention) clinical studies Used immunosuppressive drugs within 4 weeks before the first dose of study treatment, excluding nasal, inhalation or other local glucocorticoids or physiological doses of systemic glucocorticoids (i.e. no more than 10mg prednisone or equivalent dose of other glucocorticoids, or short-term (no more than 7 days) use of glucocorticoids to prevent or treat non autoimmune allergic diseases Planned to receive live attenuated vaccine within 4 weeks before the first dose of study treatment or during the study period. Note: inactivated virus vaccine for seasonal influenza is allowed within 4 weeks before the first administration, however, live attenuated influenza vaccine is not allowed | 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, CLL/SLL Documented CLL or SLL requiring treatment according to IWCLL (appendix A) after at least (clinical) partial response as best response after the following initial study treatment: venetoclax-rituximab in HOVON 140/GAIA or venetoclax-obinutuzumab in HOVON 139/GIVE or HOVON 140/GAIA WHO/ECOG performance status 0-3 (appendix C), stage 3 only if attributable to CLL Age at least 18 years Adequate BM function defined as Hemoglobin >5 mmol/l or Hb > 8 g/dL Absolute neutrophil count (ANC) >0.75 x 109/L (750/μL), unless directly attributable to CLL infiltration of the BM, proven by BM biopsy Platelet count >30 x 109/L (30,000/μL) without transfusion and irrespective whether it is attributable to CLL infiltration in the BM Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl ≥ 30ml/min (Cockcroft-Gault appendix E); Please note: in case eGFR or CrCl is <50ml/min the patient needs to be considered high risk for TLS Adequate liver function as indicated Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 3.0 x upper limit of normal (ULN) Any prior therapy with BTK inhibitor Prior treatment with venetoclax other than first line Other therapy with exception of chemo-/immunotherapy which is allowed also after venetoclax first line relapse Transformation of CLL (Richter's transformation) Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML) Malignancies other than CLL currently requiring systemic therapy or not treated in curative intention or showing signs of progression after curative treatment Known allergy to xanthine oxidase inhibitors and/or rasburicase History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components) Active bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebrand disease) Active fungal, bacterial, and/or viral infection that requires systemic therapy; Please note: active controlled as well as chronic/recurrent infections are at risk of reactivation/infection during 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): 18.0-999.0, Lymphoma, Non-Hodgkin Leukemia, Lymphocytic, Chronic, B-Cell Histologic documentation of disease: B-cell NHL or CLL requiring therapy; All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment. B cell NHL: In addition, the following disease-specific outlined below must be met a) If diffuse large B-cell lymphoma (DLBCL): received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent, b) If follicular lymphoma (FL)/ marginal zone lymphoma (MZL) (except mucosa-associated lymphoid tissue [MALT]), or Waldenstrom macroglobulinemia (WM): previously treated with at least 1 prior line of systemic therapy containing an anti-CD20 antibody, c) If mantle cell lymphoma (MCL): previously treated with at least 1 prior line of systemic therapy containing an anti-CD20 antibody. CLL or small lymphocytic lymphoma (SLL): relapsed or refractory with at least 1 prior line of systemic therapy containing a bruton tyrosine kinase inhibitor (BTKi) and for Part B: participants must have measurable disease as defined by the appropriate disease response Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1 Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia's formula [QTcF]) less than or equal to (<=) 480 milliseconds (ms) based on the average of triplicate assessments performed no more than 5 (plus minus [+ -] 3) minutes apart Women of childbearing potential must have a negative highly sensitive serum pregnancy test (Beta human chorionic gonadotropin) at screening and prior to the first dose of study drug Women must be: a) not of childbearing potential, b) of childbearing potential and practicing a highly effective, preferably user independent method of contraception (failure rate of less than (<) 1 percent (%) per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 90 days after last dose Known active central nervous system (CNS) involvement with lymphoma Prior solid-organ transplantation Either of the following: a) received an autologous stem cell transplant <=3 months before the first dose of JNJ 75348780, b) prior treatment with allogenic stem cell transplant <= 6 months before the first dose of JNJ-75348780, or has evidence of graft versus host disease that requires immunosuppressant therapy Prior chemotherapy, targeted therapy, immunotherapy or radiotherapy (with the of palliative radiation to limited sites that do not interfere with response assessment based on a sufficient number of other sites), within 2 weeks before the first administration of study drug. For investigational agents where the half-life is known, there should be a treatment-free window of at least 2 weeks or 5 half-lives, whichever is longer. For investigational agents with long half-lives a wash-out of 4 weeks is acceptable Active autoimmune disease that requires systemic immunosuppressive medications (example, chronic corticosteroid, methotrexate, or tacrolimus) | 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): 20.0-999.0, Jaw, Edentulous, Partially Diabetes ≥20 years Insulin-dependent diabetes with missing posterior maxillary tooth/teeth Residual bone height of the maxillary alveolar process between 4 and 7 mm Width of the alveolar process ≥6.5 mm Presence of mandibular occluding teeth Plasma glucose levels below 7.8 mmol/l or 140 mg/dl Contraindications to implant therapy Full mouth plaque score >25% Progressive periodontitis Acute infection in the area intended for implant placement Parafunction, bruxism, or clenching Psychiatric problems or unrealistic expectations Smoking. Previous smoker will not be excluded 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): 1.0-30.0, Down Syndrome Recurrent B Acute Lymphoblastic Leukemia Patients must be >= 1 and < 31 years at time of enrollment Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories Isolated bone marrow relapse Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes Patients with Down syndrome (DS) are eligible in the following categories Isolated bone marrow relapse Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study Patients with B-lymphoblastic lymphoma (B-LLy) Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia Patients with Philadelphia chromosome positive (Ph+) B-ALL Patients with mixed phenotype acute leukemia (MPAL) Patients with known Charcot-Marie-Tooth disease Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype Patients with active, uncontrolled infection defined as Positive bacterial blood culture within 48 hours of study enrollment Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed as long as blood cultures are negative for > 48 hours | 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, Superficial Lymphadenopathy • Patients presented with enlarged lymph nodes by clinical examination Patients who previously receive any medical treatment or chemo or radiotherapy Patients who previously underwent fine needle aspiration cytology or 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, Low Back Pain, Recurrent Included in the program Suffering from chronic low back pain (= low back pain installed for more than 2 months) Beneficiary of a social security For which his consent has been obtained in writing with regard to his participation in the protocol Bedridden or using a wheelchair Having a contraindication to performing the muscular exercises provided for in the protocol Having any other condition which, in the opinion of healthcare professionals, could affect its ability to complete the study or could present a significant risk Simultaneously participating in another clinical research protocol or having recently participated in another research for which the period has not been completed | 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, Knee Sprain (Mild) Knee Sprain (Moderate) Subject is aged ≥18 years old Subject has a recent mild (grade I) OR moderate (grade II) knee sprain The current condition of his/her knee allows the subject to resume usual physical activity Subject has been informed and is willing to sign an informed consent form Subject is willing to comply with protocol requirements and return to the study center for all clinical evaluations and required follow-up (18 weeks) Subject is affiliated to the French social security regime Non-inclusion Subject has conditions that may interfere with his/her ability to understand protocol requirements, participate in scheduled visits, or provide his/her informed consent Subject has worn a support (knee brace or articulated orthosis) since his/her recent injury Subject has resumed regular physical activity since his/her recent injury Subject has any medical condition that could impact the study at investigator's discretion | 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, Asthma; Eosinophilic Severe Asthma Late-Onset Asthma Key Written informed consent must be obtained at screening visit, before any assessment will be performed. Subjects should be able to provide informed written consent (study participation informed consent form): Able to give written informed consent prior to participation in the study, which will the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials Confirmed asthma diagnosis and severity and treatment requirements Fixed airway obstruction (FAO) where post-bronchodilator treatment ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] is below < 70% Confirmed optimized management skills (inhaler technique, education, adherence) Triggers and relevant co-morbidity have been assessed and managed Triggers such as smoking, beta-blockers, aspirin/NSAIDs, allergen exposure; Comorbidities such as rhinitis, obesity, GERD, OSA, VCD, depression/anxiety Severe asthmatics with blood eosinophils ≥150cells/ul at screening visit or ≥300cells/ul the last 12 months Patients with late-onset severe according to ERS/ATS guidelines eosinophilic asthma and fixed obstruction under the treatment of high dose of ICS+LABA±LAMA (late-onset asthma determined as age at diagnosis from 20 years and above) Patients with late-onset severe eosinophilic asthma with history ≥ 1 exacerbation the previous year under the treatment of high dose of ICS+LABA±LAMA Asthma Exacerbation: Subjects with an ongoing asthma exacerbation should have their screening and treatment initiation visit delayed until the investigator considers the subject has returned to their baseline asthma status. If the 4-week screening period has elapsed then the subject should be considered a screening failure. An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization. For subjects on maintenance oral corticosteroids, an exacerbation requiring oral corticosteroids was defined as the use of oral/systemic corticosteroids at least double the existing dose for at least 3 days Asthma exacerbation, within 6 weeks prior to screening that required hospitalization or emergency room visit Prior use of other biologics (including but not limited to Omalizumab, Reslizumab, Dupilumab, Benralizumab etc., for asthma or any other indications) that has potential to interfere/ affect disease progression, in the previous 6 months Pregnant or nursing women, or women of child-bearing potential History of malignancy of any organ system or any other serious co-morbidities defined by the treating physician Patients with a history of conditions other than asthma that could result in elevated eosinophils (e.g. hypereosinophilic syndromes, Churg-Strauss Syndrome, eosinophilic esophagitis) | 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 histologically confirmed diagnosis of CD20+ DLBCL primary central nervous system lymphoma "double-hit" 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): 18.0-999.0, Hemophilia B Mucopolysaccharidosis I Mucopolysaccharidosis II Subjects who received SB-318 under Study Protocol SB-318-1502, SB-913 under Study Protocol SB-913-1602, or SB-FIX under Study Protocol SB-FIX-1501 2. Subjects who have provided consent to participate in the LTFU study Unable to comply with study visit schedule or study visit procedures. 2. Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation 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): 18.0-85.0, Endothelial Dysfunction We recruit individuals who were referred for a routine screening in the primary prevention outpatient clinic of Attikon University hospital History of Coronary artery disease History of Peripheral Arterial Disease History of Heart failure History of Stroke hepatic failure renal failure active neoplasia poorly controlled DM, defined as Hba1C>7% | 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 Chronic Lymphocytic Leukemia Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480 milliseconds Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available at baseline as described in the protocol. This is not required for participants with chronic lymphocytic leukemia (CLL) Women of childbearing potential must agree to use a barrier method of contraception; use a highly effective preferably user-independent method of contraception; not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; not to plan to become pregnant; and not to breast-feed Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK) or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without evidence of progression or intolerable class-related toxicity will be eligible Known (active) central nervous system (CNS) involvement Received prior solid organ transplantation Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or JNJ 67856633 or excipients Toxicities from previous anti-cancer therapies that have not resolved to baseline levels, or to Grade less than (<) 2 (except for alopecia [>=Grade 2], vitiligo [Grade 2] and peripheral neuropathy [Grade 1]) | 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 CLL/SLL Subject must be able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures The time from diagnosis to consent should be ≤6 months Subject must be ≥ 18 years of age Subject must have diagnosis of CLL/SLL based upon 2018 iwCLL Guidelines Rai stage 0-2 disease without indication for treatment as defined by the 2018 iwCLL guidelines Subject must have high risk CLL as defined by any one of the following NOTCH1 mutated (classic frameshift mutation only) Unmutated V4-39 B cell receptor usage Pathogenic c-MYC mutations Complex karyotype, (by CpG/oligodeoxynucleotide stimulation) Previous exposure to any systemic anti-cancer therapy as a treatment for CLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, or investigational therapy. Note, patients treated with chemotherapy for a prior non-hematologic malignancy if more than 5 years earlier are eligible Subject with a history of malignancy except for non-melanoma skin cancers. Subjects treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll Subject requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry Subjects with a history of autoimmune hemolytic anemia or immune thrombocytopenia purpura Subject has prolymphocytic leukemia Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease) Subject requires warfarin or equivalent vitamin K antagonist Uncontrolled or active significant infection History of or suspected or confirmed PML Clinically 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. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on 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): 18.0-45.0, Anthrax Anthrax Immunisation Provide written informed consent prior to initiation of any study procedures. 2. Understand and comply with planned study procedures, including completion of the electronic memory aid, and be available for all study visits. 3. Agree to the collection of venous blood, per protocol. 4. Have adequate venous access for phlebotomies. 5. Be a male or non-pregnant female, 18 to 45 years of age, inclusive, at the time of enrollment. 6. Be in good health.* * As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, which would affect the assessment of the safety of participants or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, should be stable (not worsening) for the last 60 days (no hospitalizations, emergency room or urgent care for condition, or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change indicative of worsening/supplemental oxygen). This includes no change in chronic prescription medication, dose or frequency, indicative of worsening disease, in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, will not be considered a deviation of this criterion. Participants may be on chronic or as needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Herbals, vitamins, and supplements are permitted. 7. Have an oral temperature less than 100.0 degrees Fahrenheit. 8. Have a pulse 51 to 100 beats per minute, inclusive. 9. Have a systolic blood pressure 85 to 140 mmHg, inclusive. 10. Have a diastolic blood pressure 55 to 90 mmHg, inclusive. 11. Have a calculated body mass index (BMI) less than or equal to 35.0 kg/m2 at screening. 12. Screening laboratories are within acceptable parameters: -Random Glucose <110 mg/dL BUN <23 mg/dL Serum creatinine (female) <1.3 mg/dL Serum creatinine (male) < 1.4 mg/dL Alkaline phosphatase (female) <147 U/L Alkaline phosphatase (male) <192 U/L ALT (aka SGPT) <68 U/L AST (aka SGOT) (female) <45 U/L AST (aka SGOT) (male) < 60 U/L Total bilirubin < 1.3 mg/dL Have an acute illness*, as determined by the site principal investigator (PI) or appropriate sub-investigator, within 72 hours prior to study vaccination. *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters and systemic reactogenicity events as required by the protocol. 2. Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation.* *Including acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial. 3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.* *These oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination, or high-dose inhaled corticosteroids within 30 days prior to study vaccination, with high-dose 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 Intranasal corticosteroids are not exclusionary. Low and moderate potency topical corticosteroids are permitted. 4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination. 5. Have known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. Non-melanoma treated skin cancers are permitted. 6. Have known human immunodeficiency virus (HIV), chronic hepatitis B, or hepatitis C infection. 7. Have known hypersensitivity or allergy to any components of the study vaccines (Anthrax Vaccine Adsorbed (AVA), CPG adjuvants, aluminum, benzethonium chloride [phemerol], formaldehyde). 8. Have a history of receipt or plan to receive, while enrolled in this study, a licensed or unlicensed anthrax vaccine (except for the vaccines under study herein). 9. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).* *Adverse Events of Special Interest 10. Have a history of alcohol or drug abuse within 5 years prior to study enrollment or test positive on the screening urine test for drugs of abuse. 11. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere* with participant compliance or safety evaluations. *As determined by the site PI or appropriate sub-investigator. 12. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination. 13. Received or plan to receive a licensed, live vaccine within 30 days before or after each study vaccination. 14. Received or plan to receive a licensed, inactivated vaccine within 14 days before or after each study vaccination. 15. Have a known history of documented anthrax disease or suspected exposure to anthrax. 16. Received immunoglobulin or other blood products, except Rho(D) immunoglobulin, within 90 days prior to study vaccination. 17. Received an experimental agent* within 30 days prior to the study vaccination or expect to receive another experimental agent** during the trial-reporting period.*** *Including vaccine, drug, biologic, device, blood product, or medication. **Other than from participation in this trial. ***Approximately 12 months after the second study vaccination. 18. Are participating or plan to participate in another clinical trial with an interventional agent* that will be received during the trial-reporting period.** *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. **Approximately 12 months after the second study vaccination. 19. Female participants who are breastfeeding or plan to breastfeed from the time of the first study vaccination through 30 days after the second study vaccination. 20. Planning to donate blood within 4 months following second vaccination. 21. Planned elective surgery during study participation. 22. Member or immediate family member of the site research staff found on the delegation log. 23. Previously served in the military any time after 1990 and/or plan to enlist in the military at any time during 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, Richter Syndrome Chronic Lymphocytic Leukemia Subject must have confirmed diagnosis of CLL based upon 2018 International Workshop on CLL (IwCLL) with biopsy proven Richter's Transformation to a DLBCL subtype Subject must be ≥18 years of age Subject must be able to sign informed consent Ability and willingness to comply with the study protocol procedures Life expectancy of at least 24 weeks Subject must have an Eastern Cooperative Oncology Group performance status of ≤2 Subject must have adequate bone marrow function and meet the below thresholds prior to treatment Absolute neutrophil count of ≥1000 cell/uL Hemoglobin ≥ 7 g/dL Platelet count ≥ 30,000 cells/uL Diagnosis of Richter's Transformation not of DLBCL subtype (including but not limited to Hodgkin lymphoma, PLL) Prior therapy targeting Richter's transformation Any subject that initiates a targeted agent such as BTKi, venetoclax, or PI3K prior to enrollment (Continuation of a targeted CLL directed therapy such as a BTKi, venetoclax, or PI3K will be permitted as a bridge through screening but add on therapies or change in therapy will be exclusionary. These continuation therapies will be permitted up 72 hours prior to study initiation. Bridging therapy with steroid up to equivalent of 40mg of Dexamethasone daily will be allowed prior to study treatment and can be continued up to 24 hours prior to study treatment) Subject has undergone an allogeneic stem cell transplant for CLL within 6 months of study entry Subject has an active or presumed secondary malignancy at time of enrollment. A subject will be eligible if a previous malignancy was treated with curative intent and there is no evidence of disease recurrence for the past 3 years. Non-melanomatous and cervical squamous cell cancers are an exception and if excised will be allowed to enroll regardless of timing of excision Subject is known to be positive for HIV Active hepatitis C or hepatitis B defined by positive PCRs for viral DNA/RNA. Subjects with a positive Hep B core antibody and negative PCR, are allowed to enroll (prophylaxis is strongly encouraged and monthly monitoring of Hep B PCR is mandatory) Subject has baseline ≥ Grade 2 or greater peripheral neuropathy History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies Clinical evidence or known central nervous system involvement with transformed large cells | 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, Metastatic Prostate Neuroendocrine Carcinoma Metastatic Prostate Cancer Neuroendocrine-like prostate cancer, based on histology OR based on clinical presentation as defined by meeting one of the two below criteria. All subjects must submit their primary tumor or metastatic biopsy pathology specimens to the Duke Cancer Institute where they will be centrally reviewed by Duke Pathology. Central Duke pathologic review is not required for screening but rather for confirmation of histologic subtype. Local pathologic review is sufficient for determination. 1. Criterion 1: Presence of 1 of 3 histologically proven diagnoses: 1) Primary small cell carcinoma of the prostate, defined by classic histologic features such as small tumor cells with scanty cytoplasm, darkly stained nuclei with homogeneous chromatin pattern. The tumor cells do not form glandular structure but grow as solid sheets with frequent mitotic figures and necrosis; 2) Intermediate atypical carcinoma of the prostate, which has histologic features distinct from small cell carcinoma or adenocarcinoma. The tumor grows as solid sheets or vague glandular structures. The tumor cells have moderate amounts of cytoplasm and centrally located, round and regular nuclei with fine, granular and homogeneous chromatin. Mitosis and necrosis are absent; 3) mixed histology tumors of the prostate, containing both adenocarcinoma and neuroendocrine or small cell components. 2. Criterion 2: Presence of histologically proven adenocarcinoma of the prostate without any sign of neuroendocrine or small cell histology that is radiographically progressing despite castrate levels of testosterone (<50 ng/mL) with the following poor risk features: i. Prior progression despite therapy with either abiraterone acetate and/or enzalutamide. ii. At least one of the following: 1) Visceral metastases; 3) Bulky lymphadenopathy or pelvic mass (>5 cm); 4) Low PSA (<10 ng/mL) with high volume (>20) bone metastases; 5) Short interval (<6mo) to CRPC following initiation of hormonal therapy 6) Pathogenic alterations in two of the three following genes: TP53, RB1, and PTEN as determined by tissue or plasma tumor DNA commercial or academic assays. 7) Predominantly lytic bone metastases on imaging, 8) Presence of neuroendocrine markers on histology (positive staining of chromogranin A or synaptophysin) or in serum (abnormal high serum levels for chromogranin A or GRP) at initial diagnosis or at progression. Plus any of the following in the absence of other causes: A. elevated serum LDH (>= IULN); B. malignant hypercalcemia; C. elevated serum CEA (>2x IULN). 2. Available archival tumor tissue for pathologic review and correlative studies. Tumor tissue (localized or metastatic) does not need to be received but rather identified and available (slides and/or blocks) to be sent to Duke. 3. Documented progressive metastatic CRPC as determined by the provider based on at least one of the following 1. PSA progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2.0 ng/mL that is confirmed by another PSA level with a minimum of a 1 week interval and a minimum PSA of 2.0 ng/mL. Note: If confirmed rise is the only indication of progression, a minimal starting value of 1.0 ng/mL is acceptable, unless pure small-cell carcinoma. 2. Soft-tissue progression based on new lesions or growth of existing soft tissue metastases. 3. Progression of bone metastasis with one or more new bone lesion(s) by imaging. 4. Castrate levels of serum total testosterone (<50 ng/dl) OR ongoing documented ADT unless pure small cell prostate cancer is present. 5. Karnofsky performance status of 70 or higher. 6. Acceptable initial laboratory values within 14 days of Cycle 1 Day 1 7. Age >18 8. Subjects with a partner who is a woman of child-bearing potential must agree to use one form of highly effective contraception as detailed in Section 8.3 of this protocol during the treatment period with cabazitaxel and for 3 months after the last dose of cabazitaxel and during the treatment period with nivolumab and for 7 months after the last dose of nivolumab, whichever is later. Subjects receiving cabazitaxel or nivolumab must also refrain from donating sperm during this period. 9. Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information. 10. Life expectancy of over 3 months as determined by treating physician Prior use of abiraterone or androgen receptor antagonists (ie enzalutamide) used to treat prostate cancer are permitted but should be stopped two or more weeks prior to study treatment initiation. 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). 3. Has received other prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment initiation 4. Prior receipt of cabazitaxel chemotherapy or 2 or more chemotherapy regimens. One prior chemotherapy regimen including docetaxel or platinum-containing chemotherapy is permitted. 5. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. 6. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. 8. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 9. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. 10. Has known active untreated CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment greater than prednisone 10mg (or equivalent) for at least 14 days prior to first dose of study intervention. 11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 12. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a known uncontrolled Human Immunodeficiency Virus (HIV) infection based on detectable HIV viral load and abnormal CD4 count of <350/mm3. 15. Has a known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 16. Has a known active TB (Bacillus Tuberculosis) infection. 17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 18. Has known current psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 19. Has had an allogenic tissue/solid organ transplant | 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 Signed informed consent form (ICF). Legally Authorized Representatives are permitted Ability and willingness to comply with requirements of the study protocol ≥ 18 years-old Have documented previously untreated CLL or SLL per WHO and require treatment per iwCLL guidelines ECOG performance status of 0, 1, or 2 Participants must have adequate organ and marrow function as defined below Total bilirubin ≤ 1.5 times upper limit of normal (ULN), unless there is a disease involvement of the liver, hemolysis, or a known history of Gilbert's disease Hemoglobin ≥ 8 g/dL without transfusion support, unless anemia is due to marrow involvement of CLL Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L AST and ALT ≤ 2.5 times the ULN Prior CLL-directed therapy °Excluding corticosteroid therapy started for non-CLL related reasons or disease related symptom management (prednisone up to 20 mg daily). Topical or inhaled corticosteroids are permitted Transformation of CLL to aggressive lymphoma (Richter's transformation to NHL or Hodgkin's lymphoma, or pro-lymphocytic leukemia) CLL with deletion of chromosome 17p and/or TP53 mutation. Patients must have FISH or array CGH analysis and NGS for TP53 mutations locally as per SOC within 60 days of C1D1 (peripheral blood, bone marrow or lymph node with disease involvement are acceptable sources) as SOC History of confirmed progressive multifocal leukoencephalopathy (PML) Known hypersensitivity to any active ingredient in the study drugs Active bleeding, or presence of known bleeding disorder (e.g. von Willebrand's disease) or hemophilia Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as Clinically significant cardiac disease that includes symptomatic arrhythmia (subjects with controlled, asymptomatic atrial fibrillation or other atrial arrhythmias during screening are allowed to enroll on study) Intracranial hemorrhage, stroke within 6 months of study enrollment Symptomatic, or history of documented congestive heart failure (NY Heart Symptomatic, or history of documented congestive heart failure (NY Heart Association functional classification III-IV | 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, 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 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: with the following exceptions MCL is excluded given increased risk of tumor lysis syndrome (TLS) with venetoclax compared to other non-Hodgkin lymphomas and need for venetoclax ramp-up, dose-escalation CLL/SLL is excluded given alternative dosing of FDA-approved venetoclax for relapsed CLL/SLL and increased risk of TLS with CLL/SLL compared to other non-Hodgkin lymphomas. NOTE: Patients with known active CNS lymphoma are not eligible Relapsed and/or refractory disease after at least 1 prior treatment regimen, as follows Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anthracycline-containing regimen Indolent B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anti CD20 antibody-containing regimen Patients must have 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). NOTE: Lesions that have been irradiated cannot be included in the tumor assessment unless unequivocal tumor progression has been documented in these lesions after radiation therapy. -Age greater than or equal to18 years NOTE: Because no dosing or adverse event data are currently available on the use of polatuzumab in combination with venetoclax, ibrutinib, obinutuzumab, prednisone and Revlimid in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials 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 or anti-cancer antibodies within 2 weeks. NOTE: Short courses of corticosteroids or palliative XRT prior to enrollment are permitted within the 2- week washout period Radio or toxin-immunoconjugates within 10 weeks Previous treatment with polatuzumab or more than one of the other 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 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 to the first dose of venetoclax or ibrutinib are excluded, as noted | 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): 18.0-90.0, Lymphadenopathy Lung Cancer Sarcoidosis Tuberculosis Age >18 years at the time of the procedure Known or suspected lung cancer based on imaging (CT and/or PET/CT) Endosonography (EBUS and/or EUS) indicated for intrathoracic lymph node assessment/sampling according to national and international guidelines: 1) enlarged (> 1 cm on its short axis at CT) and/or PET positive lymph node; and/or 2) conditions at risk for occult mediastinal metastases, such as: i) central primary tumor; ii) primary tumor > 3 cm; iii) PET negative primary tumor; iv) ipsilateral hilar metastasis (cN1 status) Inability or unwillingness to consent Compromised upper airway (i.e., concomitant head and neck cancer with upper airway obstruction; critical central airway obstruction from any cause) Contraindication for temporary interruption of the use of antiplatelet (excluded aspirin) or anticoagulant drugs ASA 4 | 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, Lymphoma, Large B-Cell, Diffuse Transplantation Chemotherapy Male and female, aged 18-65; 2. newly-diagnosed high risk (aaipi 2-3 and aaipi 1 with large mass) DLBCL patients after autologous stem cell transplantation; 3. Laboratory tests (blood tests, liver and renal function) meet the following requirements: 1. Blood tests: white blood cell count ≥ 3.0 × 109 / L, absolute neutrophil count ≥ 1.5 × 109 / L, hemoglobin ≥ 90g / L, platelet ≥ 75 × 109 / L 2. Liver function: transaminase ≤ 2.5 × upper limit of normal value, bilirubin ≤ 1.5 × upper limit of normal value; 3. Renal function: serum creatinine 44-133 mmol / L; 4. The score of ECOG was 0-2; 5. The subject or his legal representative must provide written informed consent before the special examination or procedure of the study Pregnant or lactating women; 2. Severe complications or infection; 3. Lymphoma involving central nervous system; 4. Participate in other clinical trials at the same time; 5. According to the judgment of the researcher, the patients who are not suitable for this study were selected | 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, Carcinoma Breast Triple-negative Breast Cancer Invasive Ductal Carcinoma, Breast Aged from 18 to 70. 2. Histologically confirmed as breast invasive ductal carcinoma. 3. Molecular typing of breast lesions is triple-negative breast cancer, when the patient had multicentric lesions at the same time, all invasive lesions were confirmed as triple-negative. 4. Regional lymph node metastasis confirmed by postoperative pathology [except isolated tumor cells ( ITC )], or tumor response did not achieve pathological complete response (pCR) after neoadjuvant therapy [neoadjuvant chemotherapy completed at least four cycles, the breast has residual invasive cancer or axillary lymph node metastasis ( except isolated tumor cells ) .] 5. There was no local recurrence and distant metastasis of the tumor. 6. The time of randomization is during the postoperative adjuvant therapy or within 60 days after the end of the last postoperative adjuvant therapy. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1. 8. Hepatic function and renal function: serum creatinine level ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) concentration / alanine aminotransferase (ALT) concentration≤ 2.5 × ULN，total serum bilirubin concentration≤ 1.5 × ULN. 9. Blood routine: neutrophil count ≥ 1.5*109 / L, platelet count ≥ 100*109 / L, hemoglobin concentration ≥ 90 g / L (without transfusion). 10. The participants volunteered to join the study with good compliance and signed an informed consent form Bilateral breast cancer. 2. Complicated with severe cardiopathy, hepatopathy, nephropathy, endocrine system diseases. According to the researchers' judgement, the comorbidities can cause unacceptable safety risks and affect participants' compliance with research programs. 3. Suffering from malignant tumors other than breast cancer (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the past 5 years. 4. Allergic to Huaier granule. 5. Pregnant or lactating women, and those who planning a pregnancy during the study period. 6. Participating in other clinical trials or participated in other clinical studies within 3 months. 7. Patients with a poor compliance, or they are not appropriate for this study because of other reasons considered by the researchers | 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 Respiratory Failure Patient with acute respiratory failure table (SpO2 90% in ambient air or need more than 3 L/min of oxygen to have SpO2 > 92% AND/OR signs of respiratory struggle sign AND/OR respiratory rate control > 25 cycles/minute AND/OR cyanosis) Over 18 years old Pregnant, Parturising or Breastfeeding Women Patient who has already participated in the study in the previous 7 days | 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): 75.0-999.0, Ann Arbor Stage III Diffuse Large B-Cell Lymphoma Ann Arbor Stage IIX (Bulky) Diffuse Large B-Cell Lymphoma Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma Diffuse Large B-Cell Lymphoma Activated B-Cell Type Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type Diffuse Large B-Cell Lymphoma, Not Otherwise Specified EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Grade 3b Follicular Lymphoma HHV8-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements High Grade B-Cell Lymphoma, Not Otherwise Specified Intravascular Large B-Cell Lymphoma Lymphoplasmacytic Lymphoma Nodular Lymphocyte Predominant Hodgkin Lymphoma Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma Participants must have histologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL), Ann Arbor stage IIX (bulky), III or IV. Participants with DLBCL transformed from follicular lymphoma (FL) or marginal zone lymphoma (MZL, including mucosa-associated lymphoid tissue [MALT] lymphomas), lymphoplasmacytic lymphoma (LPL), or nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are eligible. Participants with grade IIIB follicular lymphoma (FL) and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are also eligible. Participants with DLBCL that arose from prior chronic lymphocytic leukemia (CLL) (Richter's transformation) are not eligible As defined by the World Health Organization (WHO), eligible lymphoma subtypes the following DLBCL, not otherwise specified (NOS) DLBCL, germinal-center B-cell type (GCB) DLBCL, activated B-cell type (ABC) T-cell histiocyte-rich B-cell lymphomas (THRBCL) Primary cutaneous DLBCL, leg type Intravascular large B cell lymphoma EBV+ DLBCL, NOS DLBCL associated with chronic inflammation Participants must not have known lymphomatous involvement of the central nervous system (CNS) Participants must not have active inflammatory bowel disease (such as, Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism, or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity Participants must not have received any prior cytotoxic chemotherapy or rituximab for treatment of the newly diagnosed DLBCL. Participants who received a short course of glucocorticoids (=< 7 days) per the pre-phase are eligible. Inhaled, nasal, and topical steroid use is allowed. Prior cytotoxic chemotherapy and/or antibody therapy for an indolent lymphoma prior to transformation is allowed Participants must not have received more than a cumulative of 250 mg/m^2 of prior anthracycline therapy (at any time prior to registration) Participants must not currently be receiving any other investigational agents Participant must not have a history of allergic reactions attributed to azacitidine, mannitol, or other hypomethylating agents Participants must not have active infection (systemic fungal, bacterial, or viral infection) that is not controlled (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment) Participants must not have active cardiac disease within 26 weeks prior to registration, including: symptomatic congestive heart failure (New York Heart Association [NYHA] class 4), unstable angina pectoris, hemodynamically unstable cardiac arrhythmia, or myocardial infarction Participants must not have >= grade 2 neuropathy, by Common Terminology for Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to registration Participants must not have any other known uncontrolled intercurrent illness including, but not limited to ongoing psychiatric illness/social situations that would limit compliance with study requirements | 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, CLL Progression All CLL patients CLL patients on treatment | 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 Small Lymphocytic Lymphoma Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma per IW-CLL 201814 requiring therapy based on at least one of the following as listed below Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 109/L) Massive (≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT 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 Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy Documented constitutional symptoms, defined as 1 or more of the following disease related symptoms or signs: unintentional weight loss >10% within 6 months prior to screening, significant fatigue (inability to work or perform usual activities), fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection, night sweats for more than 1 month prior to screening without evidence of infection Both previously untreated and relapsed or refractory patients will be eligible, including those who will be receiving venetoclax as monotherapy or in combination with anti-CD20 monoclonal antibody therapy Age greater or equal to 18 years Treatment with venetoclax within the past 6 months Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia) 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 CD20 antibody therapy (i.e. rituximab or obinutuzumab) if it is being used as part of the venetoclax regimen (see 3.1.2) 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 Active malignancy requiring therapy that would interact with venetoclax as per the discretion of the treating investigator | 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): 20.0-75.0, B-cell Acute Lymphoblastic Leukemia Non-Hodgkin's Lymphoma, Relapsed Non-Hodgkin's Lymphoma Refractory Primary Mediastinal Large B Cell Lymphoma Diffuse Large B Cell Lymphoma Follicular Lymphoma Mantle Cell Lymphoma High-grade B-cell Lymphoma for Enrollment: A subject may participate in the study if all the following is met Patients with CD19+ malignancies that are refractory to or relapsed after current standard treatment (including allogeneic or autologous HSCT) and not suitable for other treatment options, such as second-time HSCT. CD19+ malignancies 1. Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (ALL): 1. Refractory ALL is defined as failure to achieve CR at the end of induction. 2. Relapsed ALL is defined as reappearance of blasts in the blood or bone marrow (≥ 5%) or in any extramedullary site after a CR. 2. Relapsed/Refractory B-cell originated Non-Hodgkin Lymphoma (NHL) including 1) de-novo diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma, 2) large-B cell lymphoma transformed from indolent lymphomas, 3) follicular lymphoma of all grades, 4) mantle cell lymphoma, and 5) CD20(+) high-grade B-cell lymphomas. Refractory disease for lymphoma is defined as: 1. Progressive disease or stable disease lasting < 6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence < 12 months after prior autologous HSCT. 2. Prior therapy must have included an anti-CD20 monoclonal antibody-containing regimen and an anthracycline-containing chemotherapy regimen 3. For patients with transformed follicular lymphoma (TFL), prior chemotherapy for follicular lymphoma and subsequent refractory disease after transformation to DLBCL. 4. At least one measurable lesion, demonstrating that the nodal lesion is ≥ 1.5 cm in the longest diameter or the extranodal lesion is ≥ 1.0 cm in the longest diameter, according to the Lugano Classification (2014) Patients must have received at least 2 prior lines of therapy. HSCT (allogeneic or autologous) can be accounted as one of the prior line therapy, and the subjects must have been at least 3 months from prior HSCT Karnofsky Performance Scale ≥ 60 Patient able to provide written informed consent for participating in the study Age ≥ 20 years and ≤ 75 years old at the time of providing informed consent Patients shall be at least 3 weeks from the last cytotoxic chemotherapy before apheresis. Short-acting targeted therapies (e.g., tyrosine kinase inhibitors) must be stopped > 72 hours before apheresis Monoclonal antibody use including Anti-CD20 therapy has been discontinued at least 4 weeks before leukapheresis and CAR-T cells infusion except for systemic inhibitory/stimulatory immune checkpoint therapy. Immune checkpoint therapy has been discontinued at least 3 half-lives before leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc.) Absolute lymphocyte count (ALC) ≥ 1.0x109/L and absolute number of CD3+ T cells (ATC) ≥ 0.3x109/L, absolute neutrophil count (ANC) ≥ 1.0 x109/L for lymphoma and ANC ≥ 0.5 x109/L for ALL, platelets ≥ 50.0 x109/L, hemoglobin ≥ 80.0 g/L within 7 days before apheresis Adequate organ function demonstrated by the following: 1. Renal: serum creatinine <2 x upper limit of normal (ULN) 2. Hepatic: ALT/AST ≤ 2.5 x ULN or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be ≤ 3.0 mg/dL. 3. Cardiac: no clinically significant ECG findings, hemodynamically stable and LVEF ≥ 45% confirmed by echocardiogram 4. Pulmonary: baseline oxygen saturation > 90% on room air for Enrollment A subject who met any of the following is not eligible to enter the study Received previous treatment with anti-CD19 therapy Is with a history of CNS malignancy and/or active CNS diseases Has previous or concurrent malignancies other than CD19+ malignancies Has active neurological, autoimmune, or inflammatory disorders Has clinically significant cardiac diseases, or cardiac arrhythmia not controlled with medical treatment Has cardiac involvement with lymphoma Has any active infections, conditions, and diseases that may interfere with the assessment of safety and efficacy of the study deemed by the investigator or designee Received live vaccine within 6 weeks of the screening Received radiation therapy within 2 weeks of the planned CAR-T cells infusion | 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, Advanced Prostate Carcinoma born male diagnosed with advanced or metastatic prostate cancer able to read and speak English not born male not diagnosed with advanced or metastatic prostate cancer not able to read and speak English | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Generalized Epilepsy Infantile Spasms Metabolic Disease Partial Epilepsy Seizures Patients with partial seizures, infantile spasms and Lennox-Gastaut syndrome will be selected Evidence of a structural lesion as cause for epilepsy. Degenerative or metabolic disease. Inability to comply with the protocol | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Partial Epilepsy Seizures Age 5 to 60 at entry to protocol. History of partial or Complex Partial Epilepsy for two or more years. Patients should be on a stable anti-convulsant regimen defined as unchanged medicines and dose modifications lower than 20% in the last month. Blood levels of anti-convulsants will be measured at the beginning of the study, prior to stimulation and after the study to assure that the type and dose of medication will remain constant. Seizures not completely responsive to medical treatment (1 or more seizures per week for at least 6 months) and patients have failed at least two anti-convulsant regimens in the past. The patients have a localized seizure focus. Epilepsy refractory to medical treatments. No pregnant women (will be tested with urine pregnancy test). No severe coronary disease. No metal anywhere in the cranium except the mouth. No intracardiac lines. No increased intracranial pressure as expressed by the presence of papilledema. No cardiac pacemakers. Must not be taking neuroleptic or antidepressant medications. No progressive neurologic disease | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Drug/Agent Toxicity by Tissue/Organ Lymphoma Neutropenia Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific Malignant solid tumor or lymphoma refractory to standard therapy or for which no therapy of proven benefit exists No leukemia Measurable or evaluable disease Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: At least 3 months WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Heart Diseases Ventricular Arrhythmia Ventricular Fibrillation Death, Sudden, Cardiac Heart Arrest Patients with left ventricular dusfunction 2. Patients with non-ischemic cardiomyopathy Patients not at high risk for sudden cardiac death (SCD) | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 2.0-999.0, Epilepsy All patients older than 2 years referred to the Clinical Epilepsy Section will be included. DPA assignment for adults without consent capacity is required at the time of enrollment None | 2 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Epilepsy Seizure Cognition Disorders Subject must be diagnosed with partial seizures and/or secondary generalization or primary generalized seizures (absence, atonic, myoclonic, and generalized tonic-clonic seizures) Subjects must be on either carbamazepine, lamotrigine, phenytoin, or valproate monotherapy Mothers must not have a history of drug abuse (including alcohol) in the last year and have no sequelae of drug abuse Mothers must be able to maintain an accurate seizure diary of major motor seizures Subjects must have an IQ greater than or equal to 70 points Subjects must have a history of a negative RPR and HIV Subjects must not have progressive cerebral disease or presence of other major medical illness Subjects must not have exposure to known teratogens during pregnancy, except AEDs Subjects must not have poor compliance with prenatal care Subjects must have adequate reading skills to perform the cognitive tests | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 21.0-75.0, Depression Epilepsy Must have a seizure disorder Must meet the DSM-IV for major depression Must be willing to provide written informed consent Must be age 21 to 75 years old Must be compliant, cooperative, reliable, and able to follow instructions, and to visit the clinic on schedule Have active suicidal or homicidal ideation Have current alcohol or other substance abuse disorders or a history of bipolar depression or any psychotic disorder Are pregnant or lactating Are known to be hypersensitive to sertraline Have a progressive central nervous system disorder (such as a tumor or multiple sclerosis), or severe hepatic or renal disease (serum creatinine >3 mg/dl) | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Healthy of this study are normal adult volunteers who are greater than or equal to 21 years old are those who have either any medico-surgical, neurological and psychiatric illness, who have been taking any medication with potential influence on nervous system function; who have a pacemaker; an implanted medical pump; a metal plate or a metal object in the skull or eye (for example, after brain surgery); or who have a history of seizure disorder | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Epilepsy Epileptic patients who are undergoing invasive recording with implanted subdural electrodes that cover the sensorimotor cortices. Therefore, we will recruit only those patients with medically intractable epilepsy who are candidates for surgical treatment, and in whom invasive monitoring was deemed necessary for the purpose of precise localization of epileptogenic zones Patients whose electrode implantation does not cover the sensorimotor cortices | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 12.0-999.0, Epilepsy Epilepsy, Temporal Lobe Seizures Intractability: Two AEDs, one of which was either Dilantin, Tegretol, Carbatrol, or Trileptal used in appropriate doses, have failed due to inefficacy, not intolerance Frequency and Duration: Persistence of disabling seizures at 6 per year or greater for less than two years after onset, or after recurrence if initial treatment resulted in seizure freedom for 6 or more months Age: 12 years or older at baseline visit History: Simple and complex partial seizures, with or without secondarily generalized seizures beginning in childhood or later, with or without febrile convulsions earlier Absence of a history of serious cerebral insult after the age of 5; a progressive neurological disorder; mental retardation (I.Q. less than 70); psychogenic seizures; focal neurological deficits other than memory disturbances; unequivocal focal extratemporal EEG slowing or interictal spikes; or lesions on neuroimaging outside of the mesial temporal area Seizure semiology: Auras that occur in isolation and are not primary sensory other than olfactory or gustatory. Absence of initial focal motor movements other than automatisms or dystonic posturing. Presence of postictal confusion Neurological examination: No unexplained focal or lateralized neurological deficits other than memory dysfunction Baseline QOL and ancillary outcome data Adolescents QOLIE-48-AD, CHQ, CBCL, PANAS, Life Events Scale, FAC, FEICS-PC completed | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-55.0, Schizophrenia Hallucinations Have persistent auditory hallucinations History of neurological disorder Serious, unstable medical conditions (persons with hypertension or diabetes mellitus may enroll if these conditions are treated and stable) Active drug or alcohol abuse (persons may enroll if they have a history of drug or alcohol abuse provided that they do not use these substances at least 4 weeks prior to study initiation) History of seizures unrelated to drug withdrawal Estimated IQ less than 80 Have a sibling or parent with epilepsy Disorganized thought process or intellectual impairment that inhibits the ability to give an informed consent | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-45.0, Epilepsy Group A subjects will be 8 women between 18 and 45 years of age who have complex partial seizures with Type 1 catamenial seizure exacerbation as previously defined. Group B subjects will be 8 women between 18 and 45 years of age with complex partial seizures who do not meet the for catamenial seizure exacerbations. The presence or absence of Type 1 catamenial seizure exacerbation will be documented by a standard seizure calendar self-reported for at least two consecutive menstrual cycles. Patients receiving antiepileptic drug therapy will continue on their medications. All subjects must agree to use double barrier contraceptives, have an intrauterine device in place or practice abstinence during the course of the study. Patients will be recruited from the epilepsy patient population at the National Institutes of Health. Subjects in groups A and B will be matched for seizure frequency. Volunteers will be matched with the subjects in group A by age. In this pilot study, no attempt will be made to match patients according to anticonvulsant medications. The patient will be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study Any of the following conditions are cause for from the study: Any illness requiring chronic drug therapy other than antiepileptic drugs. Any history of an illness likely to be adversely affected by the trial. Psychiatric hospitalization lasting more than 2 months at any time prior to the study. Use of tricyclic antidepressants within 4 weeks prior to randomization and/or anti-psychotic drugs within 2 weeks prior to randomization. Children will not be included in this pilot study, because the profile of hormonal secretion undergoes profound changes during puberty. Use of illicit drugs, alcoholism or binge drinking as per medical history inventory. Women who are unwilling to use an alternative to oral contraceptives for contraception, (double barrier contraceptives, intrauterine device or abstinence), and establish that they are currently not pregnant by submitting to a pregnancy test. Exposure to any other investigational drug within 12 weeks prior to randomization. Any history of endocrine dysfunction. Women will be excluded if they do not have regular menstrual cycle intervals between 27 and 32 days or if they are pregnant, nursing or taking oral contraceptives or other reproductive hormones. If a need should arise to change the antiepileptic regime during the study this subject will be excluded and replaced with another patient. Women currently taking Phenobarbital or another barbiturate. Women who are unwilling to refrain from strenuous exercise during the study. Women who are unwilling to refrain from usage of herbal and soy products | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Dystonic Disorders Twenty healthy volunteers older than age 18 will be recruited for the study. Their gender, age, or ethnic origin will not provide bias for to the study. All subjects will sign an informed consent prior to participation in the trial for the trial will any current medical or surgical condition or neurological or psychiatric illnesses. Furthermore, any individual who is on medication with potential influence on nervous system function, who has a pacemaker, an implanted medical pump, a metal plate or metal object in the skull or eye (for example, after brain surgery), or who has a history of seizure disorder will be excluded from the trial | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Epilepsy Patients will be selected from the ERB, NINDS, NIH Epilepsy Clinic. Age 5 to 65 at entry to protocol. History of localization-related epilepsy for two or more years. Patients are on a stable anti-convulsant regimen defined as unchanged medicines and dose modifications lower than 20% in the last month. Blood levels of anticonvulsants will be measured at the beginning of the study, prior to stimulation and after the study to assure that the type and dose of medication will remain constant. Seizures are not completely responsive to medical treatment (1 or more seizures per week for at least 6 months) and patients have continued seizures despite best medical treatment in the past. The patients have a localized neocortical seizure focus, based on EEG and neuroimaging findings Patients will be excluded from this study if they: 1. are pregnant women (tested with urine pregnancy test). The effects of rTMS on pregnancy are unknown. 2. have severe coronary disease. 3. have increased intracranial pressure as expressed by the presence of papilledema. 4. have cardiac pacemakers. 5. take neuroleptic or antidepressant medications. 6. progressive neurologic disease | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Dystonic Disorders Nineteen patients age 18 and over with focal dystonia of the upper limbs (writer's cramp) will be recruited for the study. For patients, the only selection are the presence of focal hand dystonia. Nineteen normal subjects age 18 and over will be recruited for the control group. The controls will not have dystonia or any other neurological condition. All subjects will sign an informed consent prior to participation in the trial for the trial covering both the normal control and dystonia group will any concurrent medical or surgical condition as well as neurological or psychiatric illnesses will any individual who is on medications with potential influence of the nervous system function (antidepressants, anxiolytics, anticonvulsants, antipsychotic, antiparkinson, hypnotics, stimulants, and antihistamines). The also patients who have received Botulinum toxin injection within 3 months of starting the protocol. Furthermore, any individual who has a pacemaker, an implanted medical pump, a metal plate or metal object in the skull or eye (for example, after brain surgery), or who has a history of seizure disorder will be excluded from the trial | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 16.0-999.0, Epilepsy, Complex Partial Patient able and willing to give written informed consent or assent as appropriate in accordance with ICH and GCP guidelines Patient with newly diagnosed epilepsy who has complex partial seizures (with or without secondary generalization) Patient must have at least two well-documented, unprovoked, clinically evaluated and classified complex partial seizures or one well-documented, unprovoked, clinically evaluated and classified complex partial seizure and an abnormal EEG consistent with the diagnosis of epilepsy occurring within one year prior to enrollment Patient must have received less than 2 weeks of prior AED therapy, which will be discontinued at study entry EEG changes consistent with the diagnosis of epilepsy For patients with two well-documented, unprovoked complex partial seizures within one year prior to enrollment, the EEG results may be normal at the time of testing but, in the opinion of the Investigator, the patient has epilepsy For patients with one well-documented, unprovoked complex partial seizure within one year prior to enrollment, the EEG must be abnormal at the time of testing consistent with the diagnosis of epilepsy Patient age 16 years or greater In the opinion of the Investigator, the patient is in good health Female patients of child-bearing potential must not be pregnant (serum HCG negative) or lactating, and must be using a medically acceptable form of birth control such as abstinence, an adequate barrier method, or hormonal contraceptive; or female patients who are post-menopausal or have had surgical sterilization History of status epilepticus Patient with simple partial seizures only A history of non-epileptic seizures (e.g. metabolic or pseudo-seizures) Progressive encephalopathy or findings consistent with progressive CNS disease or lesions (e.g. infection, demyelination, tumor) Clinically significant uncontrolled medical disease in the previous two years (including unstable cardiac, hematological, hepatic, or renal disease) History of acute intermittent porphyria, glucose-6-phosphate dehydrogenase deficiency or hemolytic anemia Renal insufficiency (serum creatinine > 2 mg/dL) or impaired liver function (SGPT/ALT > two times upper limit of normal) History of renal calculi Laboratory test results which, in the opinion of the Investigator, are clinically significant abnormalities History of alcohol or drug abuse | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 3.0-10.0, Partial Seizure Disorder Subject has diagnosis of partial seizures with/without secondary generalization, supported by Observed ictal events consistent with partial seizures: With/ without secondary generalization; Documented by reliable observers of following 2: EEG at some time in past demonstrating focal abnormalities consistent with partial seizures; OR, in absence of demonstrable EEG abnormality: MRI/CT scan evidence of a focal CNS lesion consistent with partial seizures On stable dose of 1 or 2 antiepileptic drug(s) (AED) other than valproate, for at least 1 month Not taking valproate or is currently receiving valproate resulting in a trough concentration of less than 40 mcg/mL History of at least 4 partial seizures/month in 2 months prior to screening Parent/caregiver is able to keep an accurate seizure diary History of any of following: Lennox-Gastaut syndrome; Primary generalized seizures; Infantile spasms; Mixed seizure disorders including atypical absence; Myoclonic or atonic seizures; Pseudoseizures or Epilepsia Partialis Continuans (EPC) Has had status epilepticus in the past 6 months Has significant history of any of following that would confound study results: Cardiac (including clinically important abnormality on ECG); Renal; Psychiatric (including psychosurgery); Oncologic; Endocrine; Metabolic; Pancreatic; Hepatic disease (including clinical/serological history of hepatitis); Urea cycle disorder Has: Expanding CNS neoplasm; Active CNS infection; Demyelinating disease; Degenerative neurological disease; Progressive encephalopathy; or any Progressive CNS disease Has platelet count less than or equal to 100,000/mcL Has blood chemistry ALT/AST value(s) greater than or equal to 2 times upper limit of normal at screening Requires anticoagulant drug therapy Not expected to be able to maintain same dose of all pre-study AEDs, excluding valproate, throughout study Receiving systemic chemotherapy Has taken lamotrigine, felbamate, or pemoline, within past 3 months prior to screening | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Epilepsy Patients older than 18 years of age. Patients of both sexes and any race or ethnicity who have intractable epilepsy who are deemed surgical candidates and accept epilepsy surgery Patients younger than 18 years of age. Pregnant women. Patients who are not surgical candidates. Patients who do not accept epilepsy surgery. Patients with progressive neurological disorders. Patients who are unable to cooperate adequately with MEG/EEG recordings Patients who had brain surgery. Patients unable to understand and sign consent for the study | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Epilepsy Subjects of any race or ethnicity will be included in the study. Any subject who has been diagnosed with medically intractable epilepsy and is eligible for the epilepsy protocol #01-N-0139 will be evaluated for entry into this study All patients will have a seizure disorder as documented by EEG and video-EEG. Half of the patients will have radiologically documented mesial temporal sclerosis and the other half will have a brain MRI without mesial temporal sclerosis. The patients can only be on phenytoin, carbamazepine, oxcarbazepine, lamotrigine or levetiracetam, since these anti-epileptic drugs have the least or no effect on the glutamate and GABA levels in the brain. The patients can not take any other medications Healthy control subjects entering the study must be free of serious disease as determined by a standard physical and neurological examination. The control subjects can not be on any medication All subjects must be able to give informed consent allowing us to use the cerebrospinal fluid and serum for research All subjects will have to be able to refrain from chocolate, tea and coffee (low monoamine diet; Wood et al.1979) and alcohol during the one week before the study Patients must be seizure free for 48 hours prior to the lumbar tap and the MRS Subjects will be excluded if They are under the age of 18 They are female and are pregnant They have a history of medical disorders which can affect the concentration of cerebral metabolites, including diabetes mellitus, renal dysfunction, hepatic dysfunction and electrolyte abnormality They take any medication for the normal control group They take any medication, with the exception of phenytoin, carbamazepine, oxcarbazepine, lamotrigine and levetiracetam for the epilepsy patients They have a history of psychiatric and/or mood disorders They have implanted devices such as pacemakers, medication pumps or defibrillators, or metal in the cranium except for the mouth, intra-cardiac lines, a history of shrapnel injury or any other condition/device that may be contraindicated or prevent the acquisition of MRI They have a coagulopathy that prevents them from having a lumbar puncture performed They have had a seizure 48 hours prior to the MRS and the lumbar tap Subjects who cannot give informed consent allowing us to use the removed fluid for research will also be excluded | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-65.0, Epilepsy Relevant and are listed below Partial-onset seizures with or without secondary generalization. The final determination shall be made by the Investigator based on a clinical description of the seizures and previous diagnostic testing that includes, at a minimum, video/clinical EEG that captured at least one ictal event Anticipated average of 6 or more partial-onset seizures (with or without secondary generalized seizures) per month during the Baseline Phase, with no more than 30 days between seizures during the Baseline Phase Refractory to antiepileptic drugs (AEDs). Patients will be considered refractory if they have failed at least three AEDs due to lack of efficacy Receiving one to four currently marketed AEDs Be between 18 and 65 years of age at the time of lead implant Multilobar (>3 different lobes) anatomic areas of seizure onset Symptomatic generalized epilepsy Previous diagnosis of psychogenic/non-epileptic seizures Presence of implanted electrical stimulation medical device anywhere in the body (e.g., cardiac pacemakers, spinal cord stimulator) or any metallic implants in the head (e.g., aneurysm clip, cochlear implant). Vagal nerve stimulators are allowed if the device has been turned off for at least 30 days prior to the Baseline Week -12 visit and the patient agrees to have the generator explanted prior to or at the time of the Kinetra Neurostimulator implant | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 12.0-65.0, Generalized Convulsive Epilepsy Subjects with a confirmed diagnosis consistent with idiopathic generalized epilepsy experiencing myoclonic seizures (IIB) that are classifiable according to the International Classification of Epileptic Seizures. To ensure an idiopathic generalized epilepsy population, only these subjects with the diagnosis of juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE) or epilepsy with generalized tonic clonic seizures on awakening must be included Presence of at least eight days with at least one myoclonic seizure (IIB) per day during the eight weeks of the Baseline period Absence of brain lesion documented on a CT scan or MRI; if a CT scan or MRI has not been performed within the past five years before Visit 1, a CT scan (or MRI where legally required) should be performed during the Baseline period Presence of EEG features consistent with idiopathic generalized epilepsy on an EEG recorded during the Baseline period or no more than one year before Visit 1 Male/female children ≥ 12 years of age or adult ≤ 65 years of age at Visit 1 Subject on a stable dose of one standard anti-epileptic treatment for at least four weeks before Visit 1 Previous exposure to levetiracetam History of partial seizures History of convulsive or non-convulsive status epilepticus within 3 months prior to Visit 1 Subject taking vigabatrin or tiagabine, subject on felbamate with less than 18 months exposure, and subject under vagal nerve stimulation or ketogenic diet Subject taking any drug (except the concomitant AEDs) with possible CNS effects | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-65.0, Epilepsy, Partial Males/Females from 18 to 65 years of age (minimum body weight of 40 kg) Subjects with a confirmed diagnosis of epilepsy suffering from partial onset seizures whether or not secondarily generalized Subjects who have been treated for epilepsy for ≥6 months and are currently uncontrolled while being treated with 1-3 concomitant AED(s) Female subjects without childbearing potential; Female subjects with childbearing potential are eligible if they use a medically accepted non-hormonal contraceptive method Seizures occurring in clusters. Status epilepticus within 6 months of Visit 1. History of non-epileptic seizures Subjects on vigabatrin Subjects on felbamate, unless treatment has been continuous for >2 years Ongoing psychiatric disease other than mild controlled disorders Subjects with clinically significant organ dysfunction Known allergic reaction or intolerance to pyrrolidine derivatives and/or excipients Pregnant or lactating women Subjects currently taking levetiracetam (LEV) Use of benzodiazepines (for any indication) taken at a higher frequency than an average of once a week, unless counted as one of the concomitant AEDs | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-65.0, Epilepsy, Partial Males/Females from 18 to 65 years of age (minimum body weight of 40 kg) Subjects with a confirmed diagnosis of epilepsy suffering from partial onset seizures whether or not secondarily generalized Subjects who have been treated for epilepsy for ≥6 months and are currently uncontrolled while being treated with 1-3 concomitant AED(s), inclusive of LEV Female subjects without childbearing potential or those who are using an acceptable contraceptive method Seizures occurring in clusters. Status epilepticus within 6 months of Visit 1. History of non-epileptic seizures Subjects on vigabatrin Subjects on felbamate, unless treatment has been continuous for >2 years Ongoing psychiatric disease other than mild controlled disorders Subjects with clinically significant organ dysfunction Known allergic reaction or intolerance to pyrrolidine derivatives and/or excipients Pregnant or lactating women Use of benzodiazepines (for any indication) taken at a higher frequency than an average of once a week, unless counted as one of the concomitant AEDs | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Congestive Heart Failure, Atrial Fibrillation Patient is willing and able to comply with the protocol Patient is willing to sign written informed consent Patient is expected to remain available for Follow-up visits Patient age is 18 years and older patient is on a stable medication regimen (including beta blockers) for at least 4 weeks prior to enrollment Baseline patients should meet all of the following to be determined at the baseline assessment procedure within 4 weeks prior to device implantation New York Heart Association functional classification III or IV QRS duration > 130 ms Left ventricular ejection fraction < 35% measured by echocardiography left ventricular end diastolic dimension > 55 mm measured by echocardiography Patients with unstable angina or who have experienced an acute myocardial infarction or received coronary artery revascularization (CABG) or coronary angioplasty (PTCA) within 3 months prior to enrollment or who are candidates for CABG or PTCA Patients who have experienced CVA or TIA with permanent disability within 3 months prior to enrollment Patient on, or anticipated to require, intravenous inotropic drug therapy Patients with severe primary pulmonary disease (such as cor pulmonale) Post heart transplant patients and patients on an urgency list for cardiac transplantation Supine systolic blood pressure greater than 170 mm Patient who are not expected to survive for 8 months of study participation due to other medical conditions Women who are pregnant or with child bearing potential and who are not on a reliable form of birth control Serum creatinine greater than 250 mol/l Untreated hyperthyroidism | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 4.0-65.0, Generalized Convulsive Epilepsy Subject with a confirmed diagnosis consistent with idiopathic generalized epilepsy experiencing primary generalized tonic-clonic seizures (IIE) that are classifiable according to the ILAE Classification of Epileptic Seizures Presence of at least 3 PGTC seizures during the 8-week combined Baseline period Absence of brain lesion documented on a CT scan or MRI An EEG performed within 1 year of Visit 1 with features consistent with PGTC seizures or generalized idiopathic epilepsy Male/female subject, >=4 or <=65 years of age at Visit 1 Subject on a stable dose of one or two AEDs during baseline Previous exposure to levetiracetam History of partial seizures History of convulsive or non-convulsive status epilepticus while taking concomitant AEDs within three months prior to Visit 1 | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-74.0, Epilepsy at screening Adult aged between 18 years and 74 years Focal epileptic seizures with or without secondary generalization Present treatment with one or two antiepileptic drugs (constant dosage during 8 weeks baseline phase prior to initiation of treatment with zonisamide). Stimulation of the vagus nerve is permitted and will not be counted as antiepileptic drug For women of childbearing potential (postmenopausal for more than 1 year): possible pregnancy during the study can be excluded (by hysterectomy, sterilization or simultaneous application of two recognized methods of contraception (no oral contraceptives only) For male patients with partners of childbearing potential: a safe method of contraception is practiced during their study participation Written consent to participate in the study for randomisation At least 6 focal or clonicotonic seizures documented completely in a seizure diary or the patient chart during the 8 prospective or retrospective weeks baseline phase at screening Epileptic state during the past year Non-epileptic fits Generalized epilepsy More than 4 weeks of seizure freedom during baseline phase Concomitant progressive CNS disease including progressive myoclonus epilepsy Concomitant treatment with vigabatrine and / or topiramate Hepatic and/or renal insufficiency (creatine > 2mg% or GPT > 2 times ULN) Body weight ≤ 40 kg (History of) kidney stones; erythrocyturia, family history (in parents, children, brothers and sisters or grandparents) of kidney stones | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 16.0-65.0, Epilepsy Male/female from 16 to 65 years Well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification History of partial onset seizures Subjects having at least 4 partial onset seizures during the 4-week Baseline Period and at least 2 partial onset seizures during the 3 months prior to Visit 1 Subjects taking 1 or 2 concomitant Antiepileptic drugs (AED(s)) that have been at a stable dose Seizure type IA non-motor as only seizure type Seizures occurring only in clusters Status epilepticus during the last 2 years before Visit 1 History of cerebrovascular accident (CVA) Presence of any sign suggesting rapidly progressing brain disorder or brain tumor | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 16.0-65.0, Epilepsy, Focal Well-characterized focal epilepsy or epileptic syndrome according to the International League Against Epilepsy (ILAE) classification Subjects with a history of partial onset seizures Subjects having at least 4 partial onset seizures during the Baseline period and at least 2 partial onset seizures per month during the 3 months preceding Visit 1 Subjects being uncontrolled while treated by 1 or 2 concomitant Antiepileptic drug(s) AED(s) being stable Male/ female subjects from 16 to 65 years, both inclusive. Subjects under 18 years may only be included where legally permitted and ethically accepted Seizure type IA non-motor as only seizure type History or presence of seizures occurring only in clustered patterns History of cerebrovascular accident (CVA) Presence of any sign suggesting rapidly progressing brain disorder or brain tumor | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Epilepsy Criteria:medically refractory partial epilepsy financial ability to pay for higher priced food - Low BMI | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-65.0, Epilepsy To be scheduled to undergo deep brain stimulation therapy (DBS) in an attempt to treat intractable epilepsy None | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 6.0-65.0, Epilepsy Medically intractable epilepsy Subjects undergoing neurosurgical operations requiring cortical mapping Subjects NOT undergoing neurosurgical operations requiring cortical mapping | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 16.0-49.0, Refractory Epilepsy Arrhythmia Sudden Death Refractory epilepsy Other pre-existing heart conditions | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 12.0-999.0, Epilepsies, Partial Patient has a diagnosis of partial seizures with onset before age 50, and the patient's prior electroencephalography and magnetic resonance imaging studies are consistent with the diagnosis of partial seizures Patient has at least 4 complex partial seizures, but less than 25 seizures (any type), per month during the 3 months preceding randomization; for the 8 weeks preceding randomization, the seizure frequency should be confirmed from a patient diary Patient has not had an adequate response to an adequate dosage of - or was intolerant to - a minimum of 2 different AEDs Patient has (in the investigator's judgment) sufficient impairment from his/her epilepsy and/or epilepsy treatment that the potential benefits/risks of VNS therapy are warranted Patient must currently be receiving at least one AED, but not more than three AEDs, in a stable dosage regimen for at least one month before randomization Patient must be 12 years of age or older Patient must be able to provide reliable seizure counts and to complete the evaluations specified in the study procedures flow chart Patient must provide written informed consent, or legal guardian must give written permission and the minor provide written assent Patient has a history (lifetime) of having received more than 5 different AEDs Patient has had a bilateral or left cervical vagotomy Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy A VNS Therapy System implant would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient Patient is expected to require full body magnetic resonance imaging during the clinical study Patient has had a previous VNS Therapy System implant Patient has a previous neuroimaging study that demonstrates mesial temporal sclerosis, cortical dysplasia, or a suspected brain tumor | 1 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-75.0, Epilepsy Male or female patients aged 18-75. 2. Able and willing to give written informed consent in accordance with the ICH GCP Guidelines. 3. Female subjects of childbearing potential must not be pregnant (as confirmed by negative serum βHCG at screening and negative urine pregnancy test at baseline/during the study), must not be lactating and must use a medically acceptable form of contraception during the study and for at least 1 month after discontinuation of study drug. Medically acceptable contraception as defined here is the oral contraceptive pill, surgical sterilization or hormonal intrauterine device in place for at least 3 months. Women who are less than 2 years post-menopausal are considered to be of childbearing potential. 4. Focal epilepsy, with simple and/or complex partial seizures with or without secondary generalized seizures as defined by the ILAE criteria. 5. Patients with a minimum of 4 partial seizures in the 8 weeks preceding the baseline visit as adequately recorded using a seizure diary card. 6. Patients should be receiving at least 1 but no more than 2 other AEDs as concomitant medication, and the dosage should be stable for at least 8 weeks before the baseline visit History of status epilepticus within the last 5 years. 2. Patients with known significantly impaired renal function and/or severe hepatic impairment to the extent that the protocol dose titration schedule cannot be followed. Note Investigators should consult included SmPC as a guide. 3. Patients suffering from clinically significant psychiatric illness, psychological or behavioral problems which could interfere with study participation. 4. Patients with a history (within the last 12 months) of alcohol or drug abuse or dependency. 5. Patient suffering from any CNS progressive disease that may confound study interpretation, any active CNS infection, demyelinating disease or degenerative neurological disease. 6. Patients with a significant drug sensitivity or significant allergic reaction to any drug including sulfonamides. 7. Subjects considered by the Investigator to be an unsuitable candidate for receiving Zonegran or considered unlikely to comply with the protocol. 8. Any patient contraindicated for Zonegran treatment as per attached SmPC. 9. Any patient who is pregnant and/or lactating | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 5.0-15.0, Epilepsy, Rolandic Subjects whose guardians submitted written consent Subjects with more than 2 seizures in last 1 year Subjects showing one of the following additional Psychological burden due to seizure Seizure in daytime More than 3 seizures in last 6 month Convulsive seizure Abnormalities on MRI, EEG Mental retardation History of seizure relapse Seizures due to organic causes Medically serious acute or chronic disease or progressive and degenerative disorders Patients who have received an investigational medication | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 18.0-999.0, Seizures On Dilantin for seizure prophylaxis (dose determined by primary caregiver) with therapeutic Dilantin levels 2. Receiving enteral nutrition by the interrupted method at goal feeding rate 3. Age >18 4. Feeding tube in proper position, no restriction as to type of feeding tube (nasogastric, nasoduodenal, gastrostomy, jejunostomy), but both Dilantin and enteral feeding must be given through the same tube History of seizures 2. Albumin infusions necessary during study period 3. Anticipation that feedings will need to be held for more than 4 hours at a time 4. Patients that do not maintain stable Dilantin levels (< 25% variability) with the interrupted method of feeding 5. Inability to obtain consent from patient or spokesperson | 0 |
41 year old man with history of severe intellectual disability, CHF, epilepsy presenting with facial twitching on the right and generalized shaking in at his NH which required 20 mg valium to cease seizure activity. Per outside medical patient was felt to have focal epilepsy with secondary generalization, likely due to anoxic brain injury at birth, and probably related to the atrophic changes seen on MRI, particularly in the left temporal lobe. The patient first developed seizures at age 13 found by family to have a generalized convulsion. He had a second seizure two years after his first episode. He was maintained on Dilantin and phenobarbital. The patient went 20 years without another seizure. He was recently tapered off Dilantin, and it was felt that perhaps this medication was necessary to maintain him seizure free. The patient had no further events during the hospital course and was back at his baseline at the time of discharge. Full EEG reports are pending at the time of dictation. Past Medical History: Epilepsy as above, CHF, depression | eligible ages (years): 0.0-999.0, Epilepsy Seizures Epilepsies, Partial Epilepsy, Generalized Epilepsy, Tonic-Clonic Weigh >=25 kilograms Diagnosis of epilepsy within 3 months prior to study entry or recurrence of epilepsy while off of anit-epileptic drugs No more than two documented seizures during the three-month retrospective baseline phase may have experienced seizures prior to the three-month, retrospective baseline phase Patients with partial-onset seizures, with or without a secondarily generalized component, and generalized seizures, including tonic-clonic (grand mal), tonic, clonic, juvenile myoclonic epilepsy (impulsive petit mal) and myoclonic epilepsy Receiving either no other concomitant anti-epileptic drug (AED) or be on one standard AED Patients who do not have epilepsy Patients with absence (petit mal) or atypical absence seizures, epilepsia paritlis continua, cluster pattern or serial seizures Patients with progressive neurological or degenerative disorder Patients with significant history of unstable medical diseases Patients with a drug allergy or hypersensitivity to carbonic anhydrase inhibitors or sulfa drugs Patients with history of alcohol or drug abuse within past one year Patients with a history of suicide attempt within past one year | 2 |
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