Study of CD19/CD22 Chimeric Antigen Receptor T Cells in Children & Young Adults w/ Recurrent or Refractory B Cell Malignancies

PRIMARY OBJECTIVES: I. Determine the feasibility of producing CD19/CD22-CAR T cells meeting the established release criteria. II.Assess the safety of administering escalating doses of autologous CD19/CD22-CAR T cells that meet established release specifications in children and young adults with B-cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen. The following dose escalation will be used in two disease groups: 1) children and young adults with relapsed/refractory low disease burden ALL (\< 5% blasts), and 2) children and young adults with relapsed/refractory high disease burden ALL (≥5% blasts) or lymphoma: 1. Dose Level -1: 3 x 105 transduced T cells/kg (± 20%) 2. Dose Level 1: 1 x 106 transduced T cells/kg (± 20%) 3. Dose Level 2: 3 x 106 transduced T cells/kg (± 20%) 4. Dose Level 3: 1 x 107 transduced T cells/kg (± 20%) SECONDARY OBJECTIVES: I. Evaluate the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with B-acute lymphoblastic leukemia (ALL). TERTIARY OBJECTIVES: I. Analyze alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells. II. Evaluate whether subjects receiving CD19/CD22-CAR T cells relapse with loss or diminished expression of CD19 and/or CD22, when feasible. III. Measure persistence of CD19/CD22-CAR T cells in the blood, bone marrow and cerebral spinal fluid (CSF), and explore correlations between CD19/CD22-CAR T cell properties and CAR T cell efficacy and persistence. IV. Establish the utility of chromatin structure and epigenomic technology to characterize CAR T cell therapies. V. Explore the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with refractory B cell lymphoma in a non-statistical cohort due to expectations of low accrual. OUTLINE: This is a dose-escalation study of CD19/CD22-CAR T cells. Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells. After completion of study treatment, patients are followed up daily until day 14, twice weekly until day 28, at 2 and 3 months, every 3 months until month 12, every 6-12 months up to year 5, and then annually for years 6-15.