Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T Cells) for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies

PRIMARY OBJECTIVE: I. To determine the safety, toxicity and maximum tolerated dose (MTD) of EGFRt/19-28z/IL-12 CAR T-lymphocytes (EGFRt/19-28z/IL-12 CAR T cells) in patients with relapsed or refractory CD19+ aggressive hematologic malignancies. SECONDARY OBJECTIVES: I. To assess the anti-tumor efficacy of adoptively transferred EGFRt/19-28z/IL-12 T cells. II. To assess the in vivo persistence of adoptively transferred EGFRt/19-28z/IL-12 T cells. EXPLORATORY OBJECTIVES: I. To describe the cellular and cytokine microenvironment following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells. II. To characterize endogenous anti-tumor immune responses following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells. III. To summarize levels of normal B cells and the incidence of B cell aplasia following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells. IV. To determine the proportion of evaluable patients who achieve minimal residual disease (MRD)-negativity in peripheral blood and/or bone marrow. V. To assess phenotype and in vitro function of end-of-production (EOP) EGFRt/19-28z/IL-12 CAR T cells and phenotype at recovery following CAR T cell administration. OUTLINE: This is a dose-escalation study of EGFRt/19- 28z/IL-12 CAR T cells. Patients are assigned to 1 of 2 cohorts. COHORT A: Patients undergo leukapheresis prior to treatment. Patients receive EGFRt/19- 28z/IL-12 CAR T cells intravenously (IV) over 5 to 30 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET) as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial. COHORT B: Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial. After completion of study treatment, patients are followed up weekly for 4 weeks, every 4 weeks until 24 months, every 3 months thereafter for 1 year, then annually for up to 5 years, followed by long-term follow up for up to 15 years.