S0433 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Treating Older Patients With Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma

OBJECTIVES:

- Determine the 2-year progression-free survival of older patients with previously
untreated bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma
treated with iodine I 131 tositumomab in combination with rituximab, cyclophosphamide,
doxorubicin, vincristine, and prednisone.

- Determine the response rate (partial response, complete unconfirmed response, and
complete response) in patients treated with this regimen.

- Determine the 2-year progression-free survival and response rate (partial response,
complete unconfirmed response, and complete response) in B-cell lymphoma 2 (BCL-2)
positive patients treated with this regimen.

OUTLINE: This is a multicenter study.

- Rituximab and chemotherapy: Patients receive R-CHOP comprising rituximab IV over 6
hours; cyclophosphamide IV over 15-45 minutes; doxorubicin IV over 5-20 minutes; and
vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. Treatment
repeats every 21 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Patients then undergo a restaging evaluation. Patients without
progressive disease receive CHOP chemotherapy comprising cyclophosphamide, doxorubicin,
vincristine, and prednisone as outlined above. Treatment with CHOP chemotherapy repeats
every 21 days for 2 courses.

- Radiolabeled monoclonal antibody therapy: Approximately 4-8 weeks after completion of
chemotherapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose
of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo gamma scans over
a 1-week period in order to determine the correct treatment dose of iodine I 131
tositumomab. No more than 2 weeks after administration of the dosimetric dose, patients
receive tositumomab IV over 1 hour followed by a treatment dose of iodine I 131
tositumomab IV over 20 minutes.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 15 months.

DISEASE CHARACTERISTICS:

- Diagnosis of diffuse large B-cell non-Hodgkin's lymphoma, meeting 1 of the following
stage criteria:

- Bulky stage II disease

- Stage III disease

- Stage IV disease

- Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease

- Bidimensionally measurable disease

- Less than 20,000/mcL circulating lymphoid cells on white blood cell (WBC)
differential count

- Adequate sections AND a paraffin block OR ≥ 10 unstained sections from the original
diagnostic specimen available

- Needle aspiration or cytology are not considered adequate

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

- No prior diagnosis of indolent lymphoma

- No histologic transformation

PATIENT CHARACTERISTICS:

Performance status

- Zubrod 0-2

Life expectancy

- Not specified

Hematopoietic

- See Disease Characteristics

Hepatic

- Not specified

Renal

- Not specified

Cardiovascular

- Ejection fraction ≥ 45% by multiple gated acquisition scan (MUGA) OR

- No significant abnormalities by echocardiogram

Pulmonary

- No requirement for continuous supplemental oxygen

Other

- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, stage I or II cancer in complete remission, or carcinoma
in situ of the cervix

- No known HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior antibody therapy for lymphoma

Chemotherapy

- No prior chemotherapy for lymphoma

Endocrine therapy

- Not specified

Radiotherapy

- No prior radiotherapy for lymphoma

Surgery

- No prior solid organ transplantation

Other

- Concurrent enrollment on protocol SWOG-8947 (lymphoma serum repository) or protocol
SWOG-8819 (lymphoma tissue repository) is encouraged