CD19-directed CAR-T Cell Therapy for R/R Acute Leukemia and Lymphoma

Exclusion Criteria

• •For non-Hodgkin Lymphomas (B-NHL):
• •Previous or concurrent cancer distinct from B-NHL within 2 years before screening, except for the following:
• •* Curatively treated nonmelanomatous skin cancer;
• •* Curatively treated cervical carcinoma in situ;
• •* Localized breast cancer treated with curative intent with no evidence of active disease; or
• •* Localized prostate cancer undergoing active surveillance or anti-androgenic therapy, without evidence of metastatic disease.
• •Syndromes and/or genetic diseases with impact on the hematopoietic system, including Down's syndrome, Fanconi anemia, telomeropathies, Li Fraumeni, Blackfan-Diamond anemia, or congenital immunodeficiencies;
• •History of previous CAR-T therapy;
• •History of previous solid organ transplantation;
• •Active central nervous system (CNS) involvement by disease, detected by image or cytology/immunophenotyping of cerebrospinal fluid (CSF);
• •Primary central nervous system lymphoma (PCNSL);
• •Primary mediastinal large B cell lymphoma (PMBCL);
• •Evidence of uncontrolled systemic infection (viral, bacterial, or fungal) which requires IV antibiotics, within 2 weeks before the screening visit;
• •Known HIV infection;
• •Known HTLV I and II infection;
• •History of previous tuberculosis;
• •Positive Chagas disease serology;
• •Hepatitis B or hepatitis C testing indicating active/ongoing infection, as defined as:
• •* HBV: Patients with positive HBsAg are excluded. Patients with positive anti-HBc and negative HBsAg require hepatitis B PCR evaluation before randomization. Patients who are hepatitis B PCR-positive will be excluded.
• •* HCV: Patients with positive hepatitis C antibody may be enrolled with a negative result for hepatitis C RNA before study inclusion. Patients who are hepatitis C RNA-positive will be excluded.
• •History of a symptomatic CNS disease (or which required treatment within the past year), such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease;
• •Significant cardiovascular disease defined as ≥ grade 3 New York Heart Association functional classification system of heart failure, history of myocardial infarction, uncontrolled or symptomatic arrhythmias, or unstable angina within the past 6 months before the screening;
• •Chronic lung disease, with hypoxemia (Oxygen saturation measured by pulse oximetry \> 93% on room air), or uncontrolled within 4 weeks before the screening visit
• •History of an autoimmune disease (including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis) with end-organ damage or requiring systemic immunosuppression/systemic disease-modifying agents in the 2 years preceding the screening visit;
• •* Participants with hypothyroidism receiving a stable dose of thyroid replacement hormone may be eligible.
• •* Participants with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• •History of deep vein thrombosis or pulmonary embolism within 6 months before the screening visit, or need to use systemic anticoagulation at the time of screening for any other reason;
• •Major surgery within 4 weeks of the screening visit;
• •History or suspicion of hemophagocytic lymphohistiocytosis (HLH);
• •Vaccination with a live or attenuated virus vaccine within one month before the screening visit;
• •Patients with known hypersensitivity, including anaphylaxis, to any component of the investigational treatment;
• •Pregnancy, lactation, or plan to get pregnant during the study or within 12 months after CAR-T cell infusion;
• •In women of childbearing potential a negative serologic pregnancy test must be obtained 7 days before CAR-T cell infusion;
• •Women of childbearing potential, and all male participants, must be willing to observe barrier and highly effective birth control methods (outlined in the study protocol) for 12 months following CAR-T cell infusion;
• •Presence of any other medical condition that in the investigator's opinion may interfere with the safety or effectiveness evaluation of the study;
• •Life expectancy less than 12 weeks, by investigator assessment.
• •For Acute Lymphoblastic Leukemia (B-ALL)::
• •Previous or concurrent cancer distinct from B-NHL within 2 years before screening, except for the following:
• •* Curatively treated nonmelanomatous skin cancer;
• •* Curatively treated cervical carcinoma in situ;
• •* Localized breast cancer treated with curative intent with no evidence of active disease; or
• •* Localized prostate cancer undergoing active surveillance or anti-androgenic therapy, without evidence of metastatic disease.
• •Syndromes and/or genetic diseases with impact on the hematopoietic system, including Down's syndrome, Fanconi anemia, telomeropathies, Li Fraumeni, Blackfan-Diamond anemia, or congenital immunodeficiencies;
• •Isolated extramedullary disease;
• •Active central nervous system (CNS) involvement by disease (CNS-3 according to NCCN guideline), detected by cytology/immunophenotyping of cerebrospinal fluid (CSF) within 30 days from screening visit.
• •* Patients with CNS-1 and CNS-2 within 30 days from screening visit may be enrolled;
• •Burkitt's Leukemia/Lymphoma
• •Active acute or chronic graft-versus-host disease (GvHD), or controlled with immunosuppressants in the previous 12 weeks before the screening visit;
• •Failure to obtain hematologic complete remission (bone marrow with \< 5% lymphoblasts by morphologic assessment) after an anti-CD19 antibody-containing treatment (e.g. Blinatumomab);
• •History of previous CAR-T therapy;
• •History of previous solid organ transplantation;
• •Evidence of uncontrolled systemic infection (viral, bacterial, or fungal) which requires IV antibiotics, within 2 weeks before the screening visit;
• •Known HIV infection;
• •Known HTLV I and II infection;
• •History of previous tuberculosis;
• •Positive Chagas' disease serology;
• •Hepatitis B or hepatitis C testing indicating active/ongoing infection, as defined as:
• •* HBV: Patients with positive HBsAg are excluded. Patients with positive anti-HBc and negative HBsAg require hepatitis B PCR evaluation before randomization. Patients who are hepatitis B PCR-positive will be excluded.
• •* HCV: Patients with positive hepatitis C antibody may be enrolled with a negative result for hepatitis C RNA before study inclusion. Patients who are hepatitis C RNA-positive will be excluded.
• •History of a symptomatic CNS disease (or which required treatment within the past year), such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease;
• •Significant cardiovascular disease defined as ≥ grade 3 New York Heart Association functional classification system of heart failure, history of myocardial infarction, uncontrolled or symptomatic arrhythmias, or unstable angina within the past 6 months before the screening;
• •Chronic lung disease, with hypoxemia (Oxygen saturation measured by pulse oximetry \> 93% on room air), or uncontrolled within 4 weeks before the screening visit
• •History of an autoimmune disease (including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis) with end-organ damage or requiring systemic immunosuppression/systemic disease-modifying agents in the 2 years preceding the screening visit;
• •* Participants with hypothyroidism receiving a stable dose of thyroid replacement hormone may be eligible.
• •* Participants with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• •History of deep vein thrombosis or pulmonary embolism within 6 months before the screening visit, or need to use systemic anticoagulation at the time of screening for any other reason;
• •Major surgery within 4 weeks of the screening visit;
• •History or suspicion of hemophagocytic lymphohistiocytosis (HLH);
• •Vaccination with a live or attenuated virus vaccine within one month before the screening visit;
• •Patients with known hypersensitivity, including anaphylaxis, to any component of the investigational treatment;
• •Pregnancy, lactation, or plan to get pregnant during the study or within 12 months after CAR-T cell infusion;
• •In women of childbearing potential a negative serologic pregnancy test must be obtained 7 days before CAR-T cell infusion;
• •Women of childbearing potential, and all male participants, must be willing to observe barrier and highly effective birth control methods (outlined in the study protocol) for 12 months following CAR-T cell infusion;
• •Presence of any other medical condition that in the investigator's opinion may interfere with the safety or effectiveness evaluation of the study;
• •Life expectancy less than 12 weeks, by investigator assessment.