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