Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22

PRIMARY OBJECTIVES: I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD19/CD22 vector (referred to as tanCART-19/22 cells). II. Determine duration of in vivo survival of tanCART-19/22 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of tanCART-19/22TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time. SECONDARY OBJECTIVES: I. For patients with detectable disease, measure anti-tumor response due to tanCART-19/22 cell infusions. II. CD137 transgene is measured by the relative engraftment levels of tanCART-19/22 CD137 and TCR zeta cells over time. III. Estimate relative trafficking of tanCART-19/22 cells to tumor in bone marrow and lymph nodes. IV. For patients with stored or accessible tumor cells (such as patients with active chronic lymphocytic leukemia(CLL), acute lymphocytic leukemia (ALL), etc) determine tumor cell killing by tanCART-19/22 cells in vitro. V. Determine if cellular or humoral host immunity develops against the murine anti-CD19/22, and assess correlation with loss of detectable tanCART-19/20 (loss of engraftment). VI. Determine the relative subsets of tanCART-19/22 T cells (Tcm, Tem, and Treg). OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-CD19/22-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.