RATIONALE: Drugs used in chemotherapy work in 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 radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.

OBJECTIVES:

• Compare the progression-free survival and overall survival of patients with newly diagnosed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without either rituximab or iodine I 131 tositumomab (monoclonal antibody anti-B1). (CHOP chemotherapy alone arm closed to accrual as of 12/15/02)
• Compare the response rate of these patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Compare the molecular remission rates of this patient population treated with these regimens.
• Determine the incidence and time to development of human anti-mouse antibody positivity.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to whether microglobulin is greater than upper limit of normal (yes vs no). Patients are randomized to 1 of 3 treatment arms. (Arm I closed to accrual as of 12/15/02)

• Arm I (CHOP only): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)
• Arm II (CHOP + rituximab): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.
• Arm III (CHOP + tositumomab): Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.

Patients are followed on day 200, at 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 500 patients (250 per treatment arm) will be accrued for this study within 5.5 years. (Arm I closed to accrual as of 12/15/02)

DISEASE CHARACTERISTICS:

• Histologically confirmed previously untreated bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma

  • Grade I-III disease

• Cluster of differentiation antigen 20 (CD20) antigen positive

• Fewer than 5,000/mm^3 circulating lymphoid cells on a white blood cell (WBC) differential count

• Bidimensionally measurable disease

• Bone marrow aspiration and biopsy within the past 42 days

• No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Granulocyte count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No impaired cardiac status, including:

  • Severe coronary artery disease
  • Cardiomyopathy
  • Congestive heart failure
  • Serious arrhythmia

• Ejection fraction at least lower limit of normal by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram for questionable cardiac history

Other:

• No hypersensitivity to iodine
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after study participation
• HIV negative
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior monoclonal antibodies for cancer

Chemotherapy:

• No prior chemotherapy for lymphoma

  • Prior prednisone for non-lymphoma related illnesses allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for lymphoma

Surgery:

• See Disease Characteristics

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