CAR-20/19-T Cells in Patients With Relapsed Refractory B Cell Malignancies

GENERAL INCLUSION CRITERIA FOR ALL PATIENTS 1. Patients must be aged ≥18 years and ≤80 years with relapsed or refractory B-cell non-Hodgkin Lymphoma. 2. Absolute cluster of differentiation 3 (CD3) count ≥50 mm\^3. 3. Magnetic resonance imaging (MRI) brain and lumbar puncture with cerebrospinal fluid (CSF) analysis by cytology and flow cytometry without evidence of central nervous system (CNS) involvement ONLY in patients with history of CNS involvement or clinical suspicion at the time of enrollment EXCEPT Arm E subjects. 4. Measurable disease must be documented within four weeks of the time of consent defined as nodal lesions greater than 15 mm in the long axis or extranodal lesions \>10 mm in long and short axis OR bone marrow involvement that is biopsy proven for B-cell NHL (see separate criteria for CLL and primary/secondary CNS lymphoma). 5. Karnofsky performance score ≥70. 6. Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<5 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<5 x ULN, or considered not clinically significant as per the clinical PIs discretion (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease. 7. ANC≥1000 with no G-CSF within 72 hours or pegylated G-CSF within 14 days. 8. Platelets≥50,000 with no transfusion within 72 hours. 9. Adequate renal function, defined as creatinine clearance \>60 ml/min AND serum Cr≤1.5 mg/dL. a. No IV hydration within 24 hours of eligibility. b. No dialysis dependent renal failure within three months of planned CAR infusion. 10. Able to provide written informed consent. 11. Agree to practice birth control during the study. 12. Adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of ≥45% (by cardiac echocardiogram (ECHO) or multigated acquisition scan (MUGA)) and adequate pulmonary function as indicated by room air oxygen saturation of ≥92%. 13. Expected survival \>12 weeks. 14. Negative urine or serum pregnancy test in females of child bearing potential at study entry. 15. Meet criteria regarding fertility and contraception. 16. No contraindication to central line access. 17. Patient has demonstrated compliance to other therapies. Phase 1: 3+3 COHORT ELEGIBILITY CRITERIA 1. Diagnosis of B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), Mantle Cell Lymphoma, and DLBCL with associated subtypes (aggressive B-cell lymphoma, high grade B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein-Barr virus-positive (EBV+) diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation). 2. Patients must have active, measurable disease as defined and meet one of the following criteria. 1. Must have received Rituximab or another cluster of differentiation 20 (CD20) antibody and at minimum two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. 2. Relapse post-autologous transplant 3. Relapse post-allogeneic transplant 4. Patients not previously treated with CAR-T cell therapy PHASE 1b and 2 COHORT ELEGIBILITY CRITERIA ARM A: Six to nine patient expansion with 8-day manufacturing (Phase 1b) 1. Diagnosis of B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), and DLBCL with associated subtypes (aggressive B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, EBV+ diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation). 2. Patients must have active, measurable disease as defined and meet one of the following criteria: 1. Must have received Rituximab or another cluster of differentiation 20 (CD20) antibody and at minimum two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. 2. Relapse post-autologous transplant. 3. Relapse post-allogeneic transplant. 4. Relapse post-anti-cluster of differentiation 19 (CD19) CAR-T cell therapy. i. A maximum of two patients with prior CAR-T will be allowed in this cohort. ARM B: Six to nine patient expansion with 12-day manufacturing (Phase 1b) 1\. Diagnosis of B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), and DLBCL with associated subtypes (aggressive B-cell lymphoma, high grade B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, EBV+ diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation). 2\. Patients must have active, measurable disease as defined and meet one of the following criteria: 1. Must have received Rituximab or another CD20 antibody and at minimum two different chemotherapy regimens appropriate for their disease and be ineligible to receive autologous transplant. 2. Relapse post-autologous transplant. 3. Relapse post-allogeneic transplant. 4. Relapse post-anti-CD19 CAR-T cell therapy. i. A maximum of two patients with prior CAR-T will be allowed in this cohort. ARM C: 24 patient cryopreservation 8/12 flexible manufacturing arm 1. Diagnosis of B-cell NHL including Follicular Lymphoma, Marginal Zone Lymphoma (splenic, nodal, extranodal), and DLBCL with associated subtypes (aggressive B-cell lymphoma, high grade B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, EBV+ diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation). 2. Patients must have active, measurable disease as defined and meet one of the following criteria a. Must have received Rituximab or anoth