• Safety [ Designated as safety issue: Yes ]
  

• Survival and function of CD19CAR T-cells in vivo [ Designated as safety issue: No ]
  
• Comparison of two different T-cell products in the same patient in which the CD19CAR will differ only by the inclusion of the CD28 co-stimulatory endodomain [ Designated as safety issue: No ]
  
• Antitumor effects [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To evaluate the safety of autologous T-lymphocytes genetically modified to express artificial T-cell receptors (CAR) targeting the CD19 molecule (CD19CAR) in patients with refractory or relapsed low-grade B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia.

Secondary

• To measure the survival and function of CD19CAR T-cells in vivo.
• To compare two different T-cell products in the same patient in which the CD19CAR will differ only by the inclusion of the CD28 co-stimulatory endodomain.
• To measure the antitumor effects of chimeric CD19 receptor transduced autologous T-lymphocytes in these patients.

OUTLINE: Patients receive 2 infusions of CD19 chimeric receptor-expressing T-lymphocytes (CD19CAR) or CD19CAR-28 IV over 1-10 minutes on day 0.

Patients undergo blood sample collection periodically for laboratory studies. Samples are analyzed for retroviral integrants via quantitative real-time PCR; interferon-γ release using CD19 positive cells and CD19 negative target cells via ELISPOT; retroviral integrant clonality and integrant locus if transgenes detected at > 0.5% via PCR; and for the measurement of human anti-mouse antibodies (HAMA). Some samples are archived and used for future studies.

After completion of study treatment, patients are followed at 1, 2, 4, and 6 weeks, every 3 months for 1 year, every 6 months for 4 years, and then annually for up to15 years.