Anti-CD19/20/22 Chimeric Antigen Receptor T Cells (TriCAR19.20.22 T Cells) for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, and Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVE: I. To determine the safety of the treatment of relapsed/refractory non-Hodgkin lymphoma, relapsed/refractory chronic lymphocytic leukemia, lymphoid blast crisis from chronic myeloid leukemia and relapsed/refractory acute lymphoblastic leukemia with chimeric antigen receptor T cells targeting CD19/20/22 and to find the recommended phase II dose for this cellular therapy. SECONDARY OBJECTIVES: I. To describe the safety profile of the infusion of CAR-T cells targeting CD19/20/22 in relapsed/refractory non-Hodgkin lymphoma, relapsed/refractory chronic lymphocytic leukemia, lymphoid blast crisis from chronic myeloid leukemia and in relapsed/refractory acute lymphoblastic leukemia. II. To describe the toxicities related to infusion of CAR-T cells targeting CD19/20/22. III. To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19/20/22. IV. To describe the overall and progression free survival of patients with relapsed lymphoma, CLL, and ALL treated with autologous anti-CD19/CD20/CD22 CAR T-cells (TriCAR19.20.22 T cells). CORRELATIVE OBJECTIVES: I. To describe the persistence of TriCAR19.20.22 T cells, measured by flow cytometry and quantitative polymerase chain reaction (qPCR). II. To describe the T cell subpopulations of the TriCAR19.20.22 T cell product before infusion. III. To describe the changes in TriCAR19.20.22 T cells after infusion and their correlation with disease response and adverse events. IV. To investigate the correlation between changes in cytokine plasma concentrations and changes in TriCAR19.20.22 T cell subpopulations over time. V. To investigate proteomic changes in TriCAR19.20.22 T cell subpopulations over time. VI. To investigate whether antigen escape occurs in patients treated with TriCAR19.20.22. OUTLINE: This is a dose-escalation study of TriCAR19.20.22 T cells. Patients are assigned to 1 of 2 cohorts. COHORT A: Patients undergo apheresis between days -30 and -7 or days -9 and -7. Patients receive lymphodepletion chemotherapy with cyclophosphamide intravenously (IV) on day -6, fludarabine IV over 30 minutes on days -5 to -3. Patients then receive TriCAR19.20.22 T cells IV over 5-30 minutes on day 0. Patients also undergo echocardiography or multigated acquisition scan (MUGA) at baseline and blood sample collection and bone marrow biopsy and aspiration throughout the study. Additionally, patients undergo positron emission tomography (PET)/computed tomography (CT) as clinically indicated throughout the study. COHORT B: Patients undergo apheresis between days -30 and -7 or days -9 and -7. Patients receive lymphodepletion chemotherapy with cyclophosphamide IV on day -6, fludarabine IV over 30 minutes on days -5 to -3 and TriCAR19.20.22 T cells IV over 5-30 minutes on days 0 and 7. Patients also undergo echocardiography or MUGA at baseline and blood sample collection and bone marrow biopsy and aspiration throughout the study. Additionally, patients undergo PET/CT as clinically indicated throughout the study. After completion of study treatment, patients are followed for up at 7, 14, 21, 30, 60, and 90 days, at 6 and 12 months, then yearly for up to year 15.