RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy is more effective with or without rituximab in treating mantle cell lymphoma.

PURPOSE: Randomized phase II trial to compare the effectiveness of fludarabine and cyclophosphamide combined with rituximab to that of fludarabine and cyclophosphamide alone in treating patients who have mantle cell lymphoma.

Condition	Treatment or Intervention	Phase
contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma stage I mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma	Drug: cyclophosphamide  Drug: fludarabine  Drug: rituximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Australia, Victoria
      Peter MacCallum Cancer Centre, East Melbourne,  Victoria,  3002,  Australia; Recruiting
United Kingdom, England
      Derriford Hospital, Plymouth,  England,  PL6 8DH,  United Kingdom; Recruiting

Study chairs or principal investigators

Simon Rule, MD,  Study Chair,  Derriford Hospital   
John Seymour, MD,  Study Chair,  Peter MacCallum Cancer Centre, Australia   

Study ID Numbers:  CDR0000269136; NCRI-LY05; ALLG-LY05; EU-20230; NCRILG-LY05; NCT00053092
Record last reviewed:  December 2004
Last Updated:  January 7, 2005
Record first received:  January 27, 2003
ClinicalTrials.gov Identifier:  NCT00053092
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08