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Trial record 1 of 1 for:    CLL10
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FCR or BR in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00769522
Recruitment Status : Completed
First Posted : October 9, 2008
Last Update Posted : May 10, 2018
Sponsor:
Collaborators:
Roche Pharma AG
Mundipharma Pte Ltd.
Information provided by (Responsible Party):
German CLL Study Group

Tracking Information
First Submitted Date  ICMJE October 8, 2008
First Posted Date  ICMJE October 9, 2008
Last Update Posted Date May 10, 2018
Actual Study Start Date  ICMJE October 2, 2008
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2012)
Progression-free survival rate after 24 months [ Time Frame: 2008-2015 ]
estimated time point when 198 needed events for the final analysis(PD or deaths) have occured.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
Progression-free survival rate after 24 months
Change History Complete list of historical versions of study NCT00769522 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2012)
  • Minimal residual disease, complete response rates, and partial response rates [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Duration of remission [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Event-free survival [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Overall survival [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Overall response rate [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Response rates in and survival times in biological subgroups [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Toxicity rates [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Quality of life [ Time Frame: 2008-2015 ]
    done within the final analysis
  • Standard safety analysis [ Time Frame: 2008-2015 ]
    done within the final analysis
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
  • Duration of remission
  • Event-free survival
  • Overall survival
  • Minimal residual disease, complete response rates, and partial response rates
  • Response rates and survival times in biological subgroups
  • Toxicity rates
  • Quality of life
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FCR or BR in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia
Official Title  ICMJE 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
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • Biological: Rituximab

    cycle 1: 375 mg/m² i.v., day 0, q28d

    cycle 2-6: 500 mg/m² i.v., day 1, q28d

    Other Names:
    • Mabthera
    • Rituxan
  • Drug: Bendamustine
    cycle 1-6: 90mg/m² i.v., day 1-2, q28d
    Other Names:
    • Levact
    • Ribomustin
    • Treanda
  • Drug: Cyclophosphamide
    cycle 1-6: 250 mg/m² i.v., days 1-3, q28d
    Other Name: Endoxan
  • Drug: Fludarabine
    cycle 1-6: 25 mg/m² i.v., days 1-3, q28d
    Other Name: Fludura
Study Arms  ICMJE
  • Experimental: FCR
    Interventions:
    • Biological: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
  • Experimental: BR
    Interventions:
    • Biological: Rituximab
    • Drug: Bendamustine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 14, 2012)
564
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2008)
550
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00769522
Other Study ID Numbers  ICMJE CLL10
CDR0000616169 ( Other Identifier: Clinical Data Repository )
2007-007587-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party German CLL Study Group
Study Sponsor  ICMJE German CLL Study Group
Collaborators  ICMJE
  • Roche Pharma AG
  • Mundipharma Pte Ltd.
Investigators  ICMJE
Principal Investigator: Barbara Eichhorst, MD Medizinische Universitaetsklinik I at the University of Cologne
PRS Account German CLL Study Group
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP