S0801 Iodine I 131 Tositumomab, Rituximab, and Combination Chemotherapy in Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

OBJECTIVES:

• To evaluate the response rate in patients with previously untreated stage II-IV follicular non-Hodgkin lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) in combination with iodine I 131 tositumomab.
• To evaluate the toxicity of this regimen in these patients.
• To estimate the 3-year progression-free survival rate in patients treated with this regimen.
• To estimate the 5-year progression-free and overall survival rate in patients treated with this regimen.
• To assess the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive R-CHOP* comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least stable disease then proceed to consolidation therapy.

NOTE: *Patients receive R-CHOP in courses 1-4 and CHOP alone in courses 5 and 6.

• Consolidation therapy: Within 12 weeks after completion of induction therapy, patients receive tositumomab IV over 1 hour followed by a dosimetric dose of iodine I 131 tositumomab IV over 20 minutes. Patients then undergo whole body gamma camera scans over a 1-week period to determine the rate of total body clearance of radioactivity and the therapeutic dose of iodine I 131 tositumomab. Within 7-14 days after the dosimetric dose, patients receive tositumomab IV over 1 hour followed by a therapeutic dose of iodine I 131 tositumomab IV over 20 minutes. Patients with at least stable disease then proceed to maintenance therapy.
• Maintenance therapy: Beginning approximately 1 year after study entry and no more than 28 days after restaging, patients receive rituximab IV every 3 months for up to 4 years (16 courses) in the absence of disease progression or unacceptable toxicity.

After completion of maintenance therapy, patients are followed annually for up to 7 years. Patients who do not complete maintenance therapy are followed every 6 months for 2 years and then annually for up to 7 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed* grade 1, 2, or 3 follicular B-cell non-Hodgkin lymphoma meeting the following criteria:

• Bulky stage II or stage III or IV disease
• Diffuse large cell component must be < 25% of the biopsy
• Confirmed cluster of differentiation antigen 20 (CD20) antigen-positive disease NOTE: *Needle aspiration or cytology are not considered adequate for pathology review
• Patient must have unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days

• Positive biopsy performed > 42 days but < 6 months allowed
• Previously untreated disease
• Bidimensionally measurable disease
• No clinical evidence of central nervous system (CNS) involvement by lymphoma

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Cardiac ejection fraction ≥ 45% by multigated acquisition scan (MUGA) or ECHO
• No significant cardiac abnormalities
• No known HIV positivity
• No requirement for continuous supplemental oxygen therapy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of maintenance therapy

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
• No prior solid organ transplantation