Vaccine Therapy Plus Sargramostim Following Chemotherapy in Treating Patients With 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

DISEASE CHARACTERISTICS: 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 No CNS metastasis

PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 80-100% Life
expectancy: Not specified Hematopoietic: WBC greater than 2,500/mm3 Platelet count greater
than 100,000/mm3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 2.0 mg/dL
SGOT/SGPT less than 2 times normal Renal: Creatinine less than 2.0 mg/dL Other: 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 HIV negative Not pregnant
or nursing Negative pregnancy test Fertile patients must use effective contraception during
and for 6 months after the study

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for lymphoma
Chemotherapy: No prior cytotoxic chemotherapy for lymphoma Endocrine therapy: No prior
steroids for lymphoma At least 2 months since prior nonphysiologic doses of prednisone of
greater than 20 mg or equivalent No concurrent maintenance steroids or greater than 5mg of
daily prednisone or equivalent Radiotherapy: No prior radiotherapy for lymphoma Surgery:
Not specified