OBJECTIVES:

• Determine the time to treatment failure in patients with previously untreated mantle cell lymphoma treated with rituximab and CHOP chemotherapy comprising prednisone, cyclophosphamide, doxorubicin, and vincristine followed by yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8; yttrium Y 90 Zevalin®).
• Determine the response rate in patients at the completion of rituximab and CHOP and the incremental response rate after IDEC-Y2B8.
• Determine the toxicity of this regimen in these patients.
• Correlate serum rituximab levels with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• CHOP chemotherapy and rituximab: Patients receive cyclophosphamide IV, doxorubicin IV, vincristine IV, and rituximab IV on day 1 and oral prednisone on days 1-5 (R + CHOP). Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients who have responding or stable disease proceed to radioimmunotherapy.

• Radioimmunotherapy: Within 4-7 weeks after the completion of R + CHOP chemotherapy, patients receive rituximab IV and an imaging dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo whole body gamma imaging scans during the first day (2-24 hours) and the second or third day (48-72 hours) after injection. In the absence of altered biodistribution, patients receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8; yttrium Y 90 Zevalin®) IV over 10 minutes on day 8.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 57 patients will be accrued for this study within 2.8 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma with expression of bcl-1 and CD20

  • Stage II-IV disease

• Measurable or evaluable disease

  • Measurable disease defined as at least 1 bidimensionally measurable lesion at least 2 cm by imaging scan
  • A spleen at least 17 cm or having discrete filling defects by CT scan will constitute evaluable disease provided that no explanation other than lymphomatous involvement (e.g., portal hypertension or other liver disease) is likely
• No known CNS lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• WBC greater than 2,500/mm^3*
• Platelet count greater than 100,000/mm^3* NOTE: *Unless due to disease in bone marrow

Hepatic

• Bilirubin less than 1.5 mg/dL (1.5-3.0 mg/dL if due to liver involvement by lymphoma)
• ALT and AST no greater than 2.5 times upper limit of normal (unless due to liver involvement by lymphoma)

Renal

• Creatinine less than 2.0 mg/dL
• Calcium no greater than 11.5 mg/dL

Cardiovascular

• LVEF greater than 45%

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after study participation
• HIV negative
• No other malignancy except treated carcinoma in situ of the cervix or squamous cell or basal cell skin cancer or any other surgically cured malignancy from which the patient has been disease-free for at least 3 years
• No other concurrent serious medical condition or active infection that would preclude ability to deliver standard prednisone, cyclophosphamide, doxorubicin, and vincristine (CHOP) chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior corticosteroids allowed provided the course was no more than 2 weeks in duration

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified