Combination Chemotherapy Followed By Vaccine Therapy Plus Sargramostim in Treating Patients With Stage III or Stage IV Non-Hodgkin's Lymphoma

OBJECTIVES: * Compare the time to tumor progression in patients with stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with cyclophosphamide, prednisone, and vincristine followed by immunotherapy with keyhole limpet hemocyanin with or without autologous tumor-derived immunoglobulin idiotype and adjuvant sargramostim (GM-CSF). * Compare the efficacy of these immunotherapy regimens in terms of converting patients with partial response or unconfirmed complete response to clinical complete response. * Compare the safety and toxic effects of these immunotherapy regimens in this patient population. * Compare the time to treatment failure and survival of patients treated with these regimens. * Correlate the induction of idiotype-specific immune response with clinical benefits of achieving molecular remission in these patients. * Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients receive cyclophosphamide IV over 30-40 minutes and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses. At 6 months after completion of chemotherapy, patients maintaining partial response (PR), complete response (CR), or unconfirmed complete response (CRU) receive immunotherapy. Patients are stratified according to participating center and baseline disease status (PR vs CR/CRU). Patients are randomized to one of two treatment arms. * Arm I: Patients receive autologous tumor-derived immunoglobulin idiotype conjugated to keyhole limpet hemocyanin (KLH) subcutaneously (SC) on day 1 and adjuvant sargramostim (GM-CSF) SC on days 1-4 of weeks 0, 4, 8, 12, 16, 20, and 24. * Arm II: Patients receive KLH alone SC on day 1 and GM-CSF SC on days 1-4 of weeks 0, 4, 8, 12, 16, 20, and 24. Quality of life is assessed prior to first immunization, at 2-8 weeks after completion of immunizations, and then every 6 months for 30 months. Patients are followed every 3 months for 1 year and then every 6 months thereafter. Patients also enroll in a long-term follow-up study for an additional 5 years. PROJECTED ACCRUAL: A total of 360 patients (240 in arm I and 120 in arm II) will be accrued from the 480 patients biopsied for this study within 15-18 months.