Overview

This trial is active, not recruiting.

Condition leukemia
Treatments rituximab, bendamustine hydrochloride, cyclophosphamide, fludarabine phosphate
Phase phase 3
Target CD20
Sponsor German CLL Study Group
Collaborator Roche Pharma AG
Start date September 2008
End date July 2011
Trial size 564 participants
Trial identifier NCT00769522, 2007-007587-21, CDR0000616169, GCLLSG-CLL10

Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving bendamustine together with rituximab in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to see how well they work compared with bendamustine and rituximab in treating patients with previously untreated B-cell chronic lymphocytic leukemia.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive fludarabine phosphate IV and cyclophosphamide IV on days 1-3. Patients also receive rituximab IV on day 0 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
rituximab Mabthera
Given IV
cyclophosphamide Endoxan
Given IV
fludarabine phosphate Fludarabine
Given IV
(Experimental)
Patients receive bendamustine hydrochloride IV on days 1 and 2. Patients also receive rituximab as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
rituximab Mabthera
Given IV
bendamustine hydrochloride Levact
Given IV

Primary Outcomes

Measure
Progression-free survival rate after 24 months
time frame: 2008-2015

Secondary Outcomes

Measure
Minimal residual disease, complete response rates, and partial response rates
time frame: 2008-2015
Duration of remission
time frame: 2008-2015
Event-free survival
time frame: 2008-2015
Overall survival
time frame: 2008-2015
Overall response rate
time frame: 2008-2015
Response rates in and survival times in biological subgroups
time frame: 2008-2015
Toxicity rates
time frame: 2008-2015
Quality of life
time frame: 2008-2015
Standard safety analysis
time frame: 2008-2015

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria: - Binet stage C disease or stage B or A disease requiring treatment - Binet stage B or A disease meeting ≥ 1 of the following: - B-symptoms (e.g., night sweats, weight loss ≥ 10% within the past 6 months, fevers > 38°C or 100.4°F for ≥ 2 weeks without evidence of infection) or constitutional symptoms (e.g., fatigue) - Progressive lymphocytosis, defined as peripheral lymphocyte count > 5 x 10^9/L (i.e., > 50% increase over a 2-month period or doubling of peripheral blood lymphocyte count < 6 months) - Evidence of progressive marrow failure as manifested by the development/worsening of anemia and/or thrombocytopenia - Massive, progressive, or painful splenomegaly or hypersplenism - Massive lymph nodes or lymph node clusters (> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy - No 17p deletion by FISH - No aggressive B-cell cancer, such as Richter syndrome PATIENT CHARACTERISTICS: - WHO performance status 0-2 - Life expectancy ≥ 6 months - Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless directly attributable to CLL) - AST and ALT ≤ 2 times ULN (unless directly attributable to CLL) - Creatinine clearance ≥ 70 mL/min (creatinine clearance is to be calculated only in patients with serum creatinine ≥ 1.1 mg/dL) - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy - Hepatitis B and C negative - HIV negative - CIRS score > 6 or a single score of 4 for one organ category - No active secondary malignancy requiring treatment, except basal cell carcinoma or malignant tumor curatively treated by surgery, or successfully treated secondary malignancies in complete remission > 5 years prior to enrollment - No history of anaphylaxis following exposure to monoclonal antibodies - No active bacterial, viral, or fungal infection - No medical condition requiring prolonged use of oral corticosteroids (i.e., > 1 month) - No cerebral dysfunction or legal incapacity - No circumstance that would preclude completion of the study or the required follow-up PRIOR CONCURRENT THERAPY: - No prior CLL specific-chemotherapy, radiotherapy, and/or immunotherapy - Prednisolone administered immediately prior to initiation of study therapy allowed for very high lymphocyte counts - No concurrent participation in another clinical trial

Additional Information

Official title Phase III Trial of Combined Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab (FCR) Versus Bendamustine and Rituximab (BR) in Patients With Previously Untreated Chronic Lymphocytic Leukaemia
Principal investigator Barbara Eichhorst, MD
Description OBJECTIVES: - To compare the therapeutic efficacy of fludarabine phosphate, cyclophosphamide, and rituximab vs bendamustine hydrochloride and rituximab in patients with previously untreated B-cell chronic lymphocytic leukemia. - To compare the incidence of major side effects (e.g., myelosuppression) associated with these regimens in these patients. - To compare the rate of infections and secondary neoplasias in patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to country and disease stage. Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive fludarabine phosphate IV and cyclophosphamide IV on days 1-3. Patients also receive rituximab IV on day 0 of course 1 and on day 1 of courses 2-6. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. - Arm II: Patients receive bendamustine hydrochloride IV on days 1 and 2. Patients also receive rituximab as in arm I. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life questionnaires (EORTC-C30 and EURO-QOL) at baseline and then at 12, 24, 36, 48, and 60 months. After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year thereafter.
Trial information was received from ClinicalTrials.gov and was last updated in March 2012.
Information provided to ClinicalTrials.gov by German CLL Study Group.