Biological Therapy After Chemotherapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

• Determine the safety and toxicity of cellular immunotherapy with autologous CD8+ cytotoxic T-lymphocyte clones after chemotherapy comprising cyclophosphamide, vincristine, and prednisone in patients with relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma.

Secondary

• Determine the duration of in vivo persistence of adoptively transferred CD20-specific CD8+ cytotoxic T-lymphocyte clones in the absence and presence of subcutaneous interleukin-2 in these patients.
• Assess the trafficking of CD8+ cytotoxic T-lymphocyte clones to lymph nodes in these patients treated with this regimen.
• Determine immune response and tumor response in patients treated with this regimen.

OUTLINE: This is an open-label, pilot study.

• Leukapheresis: Patients undergo leukapheresis. Selected CD20-specific CD8+ cells are cultured to expand the cytotoxic T lymphocytes (CTL), which are then cloned.
• Chemotherapy:

Patients receive oral cyclophosphamide and oral prednisone on days 1-5 and vincristine IV on day 1. Courses repeat every 3-4 weeks for a total of 6 courses.

• Immune cell infusion:

Beginning 4 weeks after the last course of chemotherapy (and lymph nodes ≤ 5 cm diameter or ≤ 5,000 circulating CD20+ lymphocytes/mm^3), patients receive autologous CD8+ CTL clones IV over 30 minutes. Courses repeat every 2-5 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity. The last 6 patients receive interleukin-2 subcutaneously every 12 hours for 14 days, beginning 2 hours after the last infusion of CD8+ CTL clones.

After course 2 or 3 of immune cells, all patients undergo surgical lymph node biopsy to determine if immune cells are moving to the lymph nodes.

Patients are followed monthly for 1 year and then annually for 2 years.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Immunohistopathologically documented relapsed or refractory CD20+ indolent lymphomas or mantle cell lymphoma

• Indolent B-cell lymphomas including any of the following subtypes:

• Follicular lymphoma (grade I, II, or III)
• Small lymphocytic lymphoma or chronic lymphocytic leukemia
• Marginal zone lymphoma (splenic, nodal, and extra-nodal)
• Lymphoplasmacytoid lymphoma
• Ineligible for or unwilling to participate in other FHCRC/UWMC protocols
• Serological evidence of prior exposure to Epstein-Barr virus
• Must agree to undergo peripheral blood drawing, bone marrow biopsy, lymph node biopsy, and nuclear medicine imaging
• Must agree to cytoreductive chemotherapy if necessary to reduce lymph nodes to < 5 cm in diameter or circulating B lymphocyte counts to < 5,000/mm^3
• No pulmonary involvement
• No CNS involvement

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• At least 90 days

Hematopoietic:

• Not specified

Hepatic:

• No active hepatitis B infection

Renal:

• Not specified

Other:

• No HIV positivity
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No history of hypersensitivity reactions to murine proteins

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 months since prior rituximab, tositumomab, or ibritumomab
• No prior allogeneic stem cell transplantation
• No other concurrent immunotherapy (e.g., interferons, vaccines, or other cellular products)

Chemotherapy:

• At least 2 years since prior fludarabine or cladribine
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

• No concurrent systemic corticosteroids except to treat toxicity from chemotherapy or cellular immunotherapy

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 4 weeks since prior immunosuppressive therapy and recovered
• No concurrent pentoxifylline
• No other concurrent investigational agents