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Rituximab, Fludarabine, and Cyclophosphamide or Observation Alone in Treating Patients With Stage 0, Stage I, or Stage II Chronic Lymphocytic Leukemia

This study has been completed.
Information provided by:
German CLL Study Group Identifier:
First received: January 10, 2006
Last updated: September 23, 2016
Last verified: September 2016

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving rituximab together with fludarabine and cyclophosphamide is more effective than observation alone in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying rituximab, fludarabine, and cyclophosphamide to see how well they work compared to observation alone in treating patients with stage 0, stage I, or stage II B-cell chronic lymphocytic leukemia.

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Biological: rituximab
Drug: cyclophosphamide
Drug: fludarabine phosphate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial Comparing Early Treatment With Fludarabine/Cyclophosphamide + Rituximab Versus Deferred Treatment in Untreated Binet Stage A Patients With CLL and High Risk of Progression

Resource links provided by NLM:

Further study details as provided by German CLL Study Group:

Primary Outcome Measures:
  • Event-free survival [ Designated as safety issue: No ]
  • Development of a new prognostic staging system [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Time to progression to Binet stages B and C [ Designated as safety issue: No ]
  • Time to treatment [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Pharmacoeconomic analysis [ Designated as safety issue: No ]
  • Overall response (complete and partial) rate in patients in the early treatment arm [ Designated as safety issue: No ]
  • Percentage of patients achieving complete molecular remission in the early treatment arm [ Designated as safety issue: No ]
  • Duration of response in patients in the early treatment arm [ Designated as safety issue: No ]
  • Adverse events in patients in the early treatment arm [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: October 2005
Study Completion Date: June 2015
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Detailed Description:



  • Compare the effect, in terms of event-free survival, of deferred versus immediate treatment with rituximab, fludarabine, and cyclophosphamide in patients with previously untreated Binet stage A chronic lymphocytic leukemia at high risk for disease progression.
  • Investigate and define a new prognostic staging system for patients with Binet stage A chronic lymphocytic leukemia.


  • Compare the time to progression to Binet stages B and C in patients treated with these regimens.
  • Compare the overall and progression-free survival of patients treated with these regimens.
  • Compare the quality of life of patients treated with these regimens.
  • Compare the time to treatment in patients treated with these regimens.
  • Analyze the pharmacoeconomics of these regimens in these patients.
  • Determine the overall response rate (partial and complete) in patients included in the early treatment arm.
  • For patients included in the early treatment arm in complete remission, determine the percentage achieving complete molecular remission using the clone-specific CDR-III region as follow-up parameter.
  • Determine the duration of response in patients included in the early treatment arm.
  • Determine any adverse events related to treatment/safety of treatment.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk factor profile (< 2 risk factors [low risk] vs ≥ 2 risk factors [high risk]). Low-risk patients are assigned to arm II. High-risk patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive rituximab IV on day 1, fludarabine IV on days 1-3, and cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for up to 6 courses.
  • Arm II: Patients undergo observation only until disease progression.

PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Established diagnosis of B-cell chronic lymphocytic leukemia

    • First diagnosis within 12 months before inclusion in study
    • Previously untreated disease
  • Binet stage A disease (Rai stage 0, I, or II)


  • Life expectancy > 6 months
  • ECOG performance status 0-2
  • Willingness to accept contraception (if randomized to arm I) for the duration of therapy and 12 months thereafter
  • Negative serum pregnancy test
  • All parameters for risk stratification (lymphocyte doubling time, cytogenetics, unmutated IgVH, and serum thymidine kinase level > 10) present


  • No prior chemotherapy, radiotherapy, or antibody treatment
  • No other concurrent chemotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00275054

  Show 91 Study Locations
Sponsors and Collaborators
German CLL Study Group
Principal Investigator: Michael Hallek, MD Medizinische Universitaetsklinik I at the University of Cologne
  More Information

Additional Information: Identifier: NCT00275054     History of Changes
Other Study ID Numbers: CLL7  EU-20559  ROCHE-GCLLSG-CLL7  2005-003018-14 
Study First Received: January 10, 2006
Last Updated: September 23, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by German CLL Study Group:
stage 0 chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents processed this record on September 28, 2016