OBJECTIVES: I. Determine whether etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) followed by immunotherapy with autologous tumor-derived immunoglobulin idiotype conjugated to keyhole limpet hemocyanin plus sargramostim (GM-CSF) is associated with 36-month median progression-free survival in patients with previously untreated mantle cell lymphoma.

II. Assess whether idiotype vaccine generates tumor-specific T-cell response in this patient population.

III. Determine the response rate in these patients receiving this treatment. IV. Determine the toxicity of EPOCH-R in these patients.

PROTOCOL OUTLINE: Patients receive rituximab IV on day 1 immediately followed by doxorubicin, etoposide, and vincristine IV over 96 hours on days 1-4, oral prednisone twice daily on days 1-5, and cyclophosphamide IV over 15 minutes on day 5. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Treatment repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity. Patients with stable disease or a complete response receive 2 additional courses of therapy with a maximum of 6 courses.

Beginning at least 12 weeks after completion of chemotherapy and rituximab, patients receive vaccination with autologous tumor-derived immunoglobulin idiotype-keyhole limpet hemocyanin conjugate SC on day 1 and sargramostim (GM-CSF) SC on days 0-3 at weeks 12, 16, 20, 24, and 32 for a total of 5 courses.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL:

A total of 26 patients will be accrued for this study within 2 years.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Histologically confirmed mantle cell lymphoma Blastic cell variant allowed All stages of disease Chemotherapy naive Lymph node at least 2 cm accessible for biopsy/harvest OR Greater than 1,000/mm3 of circulating tumor cells in the blood No CNS involvement by lymphoma --Prior/Concurrent Therapy-- Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: Prior short course of steroids for symptom control allowed Radiotherapy: Prior local radiotherapy for symptom control allowed Surgery: Not specified --Patient Characteristics-- Age: 18 and over Performance status: ECOG 0-3 Life expectancy: Not specified Hematopoietic: Unless due to lymphoma: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 2 mg/dL (5 mg/dL for Gilbert's syndrome as defined by more than 80% unconjugated) Hepatitis B surface antigen negative Renal: Unless due to lymphoma: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No active symptomatic ischemic heart disease No myocardial infarction or congestive heart failure within the past year Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No prior malignancy within the past 5 years except basal or squamous cell skin cancer or curatively treated carcinoma in situ of the cervix