Vaccine Therapy Plus Sargramostim Following Chemotherapy in Previously Untreated Aggressive Non-Hodgkin's Lymphoma

OBJECTIVES: I. Determine the ability of recombinant idiotype immunotherapy to stimulate a specific immune response against the B cell idiotype of the malignant clone that constitutes the tumor in patients with previously untreated aggressive non-Hodgkin's lymphoma. II. Determine the safety and toxicity of this treatment regimen using Genitope Corporation's molecular rescue technology in this patient population.

OUTLINE: Patients receive induction chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). Treatment repeats every 3 weeks until the maximal clinical response is achieved followed by 2 additional courses of consolidation therapy for up to a maximum of 6 courses. At 2-6 months following completion of chemotherapy, patients achieving adequate disease response receive vaccination consisting of recombinant tumor derived immunoglobulin idiotype with keyhole limpet hemocyanin conjugate subcutaneously (SQ) followed by sargramostim (GM-CSF) SQ, each at 2 separate sites on day 1. Patients receive GM-CSF alone on days 2-4. Vaccination repeats every 4 weeks for 4 doses, followed 3 months later by the fifth and final dose. Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: Not specified

Inclusion criteria

• Histologically confirmed aggressive non-Hodgkin's lymphoma

• Diffuse mixed cell
• Diffuse large cell
• Immunoblastic Follicular large cell with more than 50% large cells
• Mantle cell
• Non-age adjusted International Prognostic Index 2-4
• Tumor sample safely accessible by biopsy, needle aspiration, or phlebotomy
• Must have adequate circulating lymphoma cells
• Over 18 years old
• Karnofsky 80-100%
• WBC greater than 2,500/mm3
• Platelet count greater than 100,000/mm3
• Hemoglobin at least 10 g/dL
• Bilirubin less than 2.0 mg/dL SGOT/SGPT less than 2 times normal
• Creatinine less than 2.0 mg/dL
• Fertile patients must use effective contraception during and for 6 months after the study
• At least 2 months since prior nonphysiologic doses of prednisone of greater than 20 mg or equivalent
• HIV negative

Exclusion criteria

• No CNS metastasis
• No other illness or condition, including innate or pharmacologic immunosuppression, that would preclude study
• No other malignancy within the last 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
• Not pregnant or nursing/negative pregnancy test
• No prior biologic therapy for lymphoma
• No prior cytotoxic chemotherapy for lymphoma
• No prior steroids for lymphoma
• No concurrent maintenance steroids or greater than 5mg of daily prednisone or equivalent
• No prior radiotherapy for lymphoma