• Toxicity [ Designated as safety issue: Yes ]
  
• Persistence of genetically modified T cells in blood, marrow, and lymph nodes following T cell infusions [ Designated as safety issue: No ]
  
• Complete and partial response [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To assess the feasibility, safety, and toxicity of cellular immunotherapy utilizing ex-vivo expanded autologous T cells genetically modified to express a "second generation" CD20-specific scFvFc:CD28:CD137:ζ (zeda) chimeric immunoreceptor in patients with recurrent or refractory CD20+ mantle cell or indolent lymphoma.

Secondary

• To determine the duration of in vivo persistence of adoptively transferred CD20-specific T cells transfected with a CD20-specific scFvFc:CD28:CD137:ζ chimeric immunoreceptor.
• To assess the trafficking of CD20-specific T cells to lymphoma masses.
• To evaluate the development of host anti-CD20 scFvFc:CD28:CD137:ζ chimeric immunoreceptor and anti-NeoR immune responses in these patients.

OUTLINE:

• Leukapheresis: Patients undergo up to 3 leukapheresis procedures, each lasting over 2-4 hours. The leukapheresis product(s) are purified, transfected, screened, and expanded to generate CD20-specific T cells.

Patients with a large tumor burden or actively growing lymphoma undergo cytoreductive chemotherapy (by referring community oncologist) to reduce the tumor burden, after leukapheresis and before lymphodepleting therapy.

• Lymphodepleting therapy: Beginning 6 days prior to T cell infusion, patients receive fludarabine phosphate IV for 5 days.
• CD20-specific T cell infusion: Beginning 1 day after completion of lymphodepletion (and at least 4 weeks after cytoreductive chemotherapy), patients receive autologous CD20-specific T-cells (generated from the leukapheresis product) IV over 30 minutes at 2-5 days interval for 3 doses.
• Maintenance (low-dose aldesleukin): Beginning approximately 2 hours after last dose of T-cell infusion, patients receive low-dose aldesleukin subcutaneously twice daily for 14 days.

Treatment continues in the absence of progressive disease or unacceptable toxicity.

Patients with pathologic lymphadenopathy undergo excisional lymph node biopsy of a superficial lymph node or core needle biopsy 24-48 hours following the second or third T-cell infusion. All patients undergo bone marrow biopsy and aspiration 24-48 hours following the final T-cell infusion. Samples are analyzed for DNA isolation and PCR evaluation to identify the chimeric gene sequence. Blood samples are collected 18-24 hours after each T cell infusion, for direct assay of peripheral blood lymphocytes for vector DNA by PCR and expression of chimeric T cell receptor by western blot.

After completion of study treatment, patients are followed weekly for 1 month and then periodically for up to 2 years.