Vaccine Therapy Plus Sargramostim Following Chemotherapy in Treating Patients With Stage III or Stage IV 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 stage III or IV indolent 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 oral cyclophosphamide,
vincristine, and prednisone (CVP). 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 10 courses. Patients not achieving adequate response receive up to 6 courses of
alternate chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and
prednisone. At 3 months or up to 1 year 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)
at 2 sites immediately followed by sargramostim (GM-CSF) SQ on day 1. Patients receive GM-CSF
alone on days 2-4. Vaccination repeats every 4 weeks for 4 doses, followed 12 weeks 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 stage III or IV, indolent non-Hodgkin's
lymphoma Follicular small cleaved cell Follicular mixed small cleaved and large cell with
less than 50% large cells No intermediate, high grade, or other non-Hodgkin's lymphomas
(e.g., mantle cell, monocytoid B cell, marginal zone, small lymphocytic, chronic
lymphocytic leukemia, or follicular large cell) Tumor sample safely accessible by biopsy,
needle aspiration, or phlebotomy Must have adequate circulating lymphoma cells No CNS
metastasis A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by
PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former
terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses
the former terminology.

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 mg/dL SGOT/SGPT
less than 2 times normal Renal: Creatinine less than 2 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

PRIOR CONCURRENT THERAPY: Biologic: No prior biologic therapy for lymphoma Chemotherapy: No
prior cytotoxic therapy for lymphoma Endocrine: 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 5 mg of daily prednisone or equivalent
Radiotherapy: No prior radiotherapy for lymphoma Surgery: Not specified