S0016 Combination Chemotherapy With Monoclonal Antibody Therapy in 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