RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining chemotherapy, monoclonal antibody therapy, and vaccine therapy may be an effective treatment for mantle cell lymphoma.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy and monoclonal antibody therapy plus vaccine therapy in treating patients who have mantle cell lymphoma that has not been previously treated with chemotherapy.

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.

• Noncontiguous Stage II Mantle Cell Lymphoma
• Stage IV Mantle Cell Lymphoma
• Contiguous Stage II Mantle Cell Lymphoma
• Stage I Mantle Cell Lymphoma
• Stage III Mantle Cell Lymphoma

• Drug: autologous tumor cell vaccine
• Drug: cyclophosphamide
• Drug: doxorubicin
• Drug: etoposide
• Drug: filgrastim
• Drug: keyhole limpet hemocyanin
• Drug: prednisone
• Drug: rituximab
• Drug: sargramostim
• Drug: vincristine

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