RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Vaccines may make the body build an immune response to kill cancer cells. It is not yet known which regimen of chemotherapy combined with vaccine therapy is more effective for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy followed by vaccine therapy plus sargramostim in treating patients who have 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.

• Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine
• Biological: keyhole limpet hemocyanin
• Biological: sargramostim
• Drug: cyclophosphamide
• Drug: prednisone
• Drug: vincristine sulfate

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV follicular B-cell non-Hodgkin's lymphoma
• At least 1 bidimensionally measurable lesion by radiography, in addition to lesion removed for biopsy
• No clinical evidence of CNS involvement

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal:

• Creatinine less than 1.5 times ULN

Other:

• No other malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of autoimmune disease
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior antibody therapy for lymphoma

Chemotherapy:

• No prior cytotoxic therapy for lymphoma

Endocrine therapy:

• No prior corticosteroids for lymphoma
• At least 12 months since prior corticosteroids or immunosuppressants for other conditions
• Prior transient corticosteroids (prior to CT imaging) or optical solutions allowed

Radiotherapy:

• Prior radiotherapy for lymphoma (no more than 2 sites of limited disease) allowed

Surgery:

• See Disease Characteristics

Other:

• No concurrent participation in other therapeutic clinical trial