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. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial of vaccine therapy plus sargramostim following chemotherapy in treating patients who have previously untreated aggressive 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 aggressive 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 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). 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 6 courses. At 2-6 months 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) followed by sargramostim (GM-CSF) SQ, each at 2 separate sites on day 1. Patients receive GM-CSF alone on days 2-4. Vaccination repeats every 4 weeks for 4 doses, followed 3 months 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

Inclusion Criteria:

• Histologically confirmed aggressive non-Hodgkin's lymphoma

  • Diffuse mixed cell
  • Diffuse large cell
  • Immunoblastic Follicular large cell with more than 50% large cells
  • Mantle cell

• Non-age adjusted International Prognostic Index 2-4

• Tumor sample safely accessible by biopsy, needle aspiration, or phlebotomy

• Must have adequate circulating lymphoma cells

• Over 18 years old

• Karnofsky 80-100%

• WBC greater than 2,500/mm3

• Platelet count greater than 100,000/mm3

• Hemoglobin at least 10 g/dL

• Bilirubin less than 2.0 mg/dL SGOT/SGPT less than 2 times normal

• Creatinine less than 2.0 mg/dL

• Fertile patients must use effective contraception during and for 6 months after the study

• At least 2 months since prior nonphysiologic doses of prednisone of greater than 20 mg or equivalent

• HIV negative

Exclusion Criteria:

• No CNS metastasis
• 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
• Not pregnant or nursing/negative pregnancy test
• No prior biologic therapy for lymphoma
• No prior cytotoxic chemotherapy for lymphoma
• No prior steroids for lymphoma
• No concurrent maintenance steroids or greater than 5mg of daily prednisone or equivalent
• No prior radiotherapy for lymphoma