• Response rate [ Designated as safety issue: No ]
  
• Time to disease progression [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Overall survival [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the response rates in patients with previously untreated mantle cell lymphoma treated with fludarabine and cyclophosphamide with or without rituximab.
• Compare the time to disease progression in patients treated with these regimens.
• Compare the toxicity of these regimens, in terms of adverse event profile, in these patients.
• Compare the overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms:

• Arm I: Patients receive fludarabine IV* and cyclophosphamide IV* on days 1-3.
• Arm II: Patients receive rituximab IV on day 1 and fludarabine IV* and cyclophosphamide IV* on days 2-4.

NOTE: *In both arms, fludarabine and cyclophosphamide may be administered orally instead of IV.

Treatment repeats every 28 days for 2-8 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 56-82 patients (28-41 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed previously untreated mantle cell lymphoma requiring therapy

  • Any stage

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• At least 3 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)^*
• Alkaline phosphatase no greater than 2.5 times ULN^*
• Hepatitis B and hepatitis C negative NOTE: *Unless related to lymphoma

Renal

• Creatinine no greater than 2.5 times ULN^* NOTE: *Unless related to lymphoma

Other

• No other malignancy within the past 5 years except non-melanoma skin cancer or curatively resected carcinoma in situ of the cervix
• No prior psychological illness or condition that would preclude study compliance
• No known hypersensitivity to murine proteins
• No concurrent uncontrolled medical conditions
• No other illness that would severely limit life expectancy
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified