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Chlorambucil in Treating Patients With Advanced Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00017108
Recruitment Status : Unknown
Verified June 2004 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : July 24, 2008
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which chlorambucil regimen is more effective in treating advanced chronic lymphocytic leukemia.

PURPOSE: Randomized phase III trial to determine the effectiveness of different regimens of chlorambucil in treating patients who have advanced chronic lymphocytic leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Drug: chlorambucil Drug: cyclophosphamide Drug: fludarabine phosphate Phase 3

Detailed Description:


  • Compare overall and disease-related survival of patients with B-cell chronic lymphocytic leukemia treated with high-dose chlorambucil induction therapy with or without low-dose chlorambucil maintenance therapy.
  • Compare the time to salvage treatment in these patients treated with these regimens.
  • Compare the toxic effects of these regimens in these patients.
  • Compare the treatment-related mortality of these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, time to complete response (before 12 weeks vs after 12 weeks vs partial response), and cytopenia at diagnosis (Binet stage A+B vs C).

All patients receive induction therapy comprising high-dose oral chlorambucil daily. Treatment continues until achievement of complete response or a maximum of 24 weeks in the absence of disease progression or unacceptable toxicity.

Patients who respond to induction therapy are randomized to 1 of 2 treatment arms for maintenance therapy.

  • Arm I: Patients receive low-dose oral chlorambucil twice a week. Therapy continues for up to 5 years in the absence of disease progression or unacceptable toxicity. If disease progression occurs, then patients may proceed to salvage therapy.
  • Arm II: Patients receive no maintenance therapy. If disease progresses, patients receive induction therapy again. If disease does not respond to re-induction therapy, then patients may proceed to salvage therapy.
  • Salvage therapy: Patients with progressive disease during maintenance therapy receive fludarabine IV daily and cyclophosphamide IV daily on days 1-3. Treatment repeats every 4 weeks for 3-6 courses.

Patients are followed monthly for 3 months, every 2 months for 6 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 470 patients will be accrued for this study within 4.7 years.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Low Dose Chlorambucil Maintenance Vs. No Treatment Following High-Dose Chlorambucil Induction In Patients With Advanced B-Chronic Lymphocytic Leukemia. A Randomized Phase III Study Of The EORTC LG (CLL-3)
Study Start Date : March 2001

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of B-cell chronic lymphocytic leukemia

    • Co-expression of CD5/CD19 or CD5/CD20 positivity, dim sIg, and CD23 positivity
    • Previously untreated advanced disease defined as presence of at least 1 of the following:

      • Total tumor mass (TTM) score greater than 9
      • TTM doubling time less than 12 months
      • Bone marrow failure (platelet count less than 100,000/mm^3 and/or hemoglobin less than 10 g/dL)



  • 18 to 75

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified


  • See Disease Characteristics


  • Bilirubin less than 3 times upper limit of normal (ULN)
  • Hepatitis B negative
  • No active hepatitis C


  • Creatinine less than 3 times ULN OR
  • Creatinine clearance greater than 0.5 times normal


  • No severe cardiovascular disease
  • No arrhythmia requiring chronic treatment
  • No New York Heart Association class III or IV congestive heart failure
  • No symptomatic ischemic heart disease


  • No uncontrolled systemic infection
  • HIV negative
  • No prior or concurrent uncontrolled malignancy
  • No prior or concurrent central nervous system or psychiatric disorders requiring hospitalization
  • No psychological, familial, sociological, or geographical condition that would preclude study participation


Biologic therapy:

  • No prior biologic therapy


  • No prior chemotherapy

Endocrine therapy:

  • Prior steroid therapy for less than 2 weeks allowed


  • No prior radiotherapy


  • Not specified

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00017108

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Hopital Universitaire Erasme
Brussels, Belgium, 1070
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
Hopital de Jolimont
Haine Saint Paul, Belgium, 7100
Czech Republic
University Hospital - Olomouc
Olomouc, Czech Republic, 775 20
County Hospital
Kaposvar, Hungary, H-7400
Azienda Ospedaliera Papardo
Messina, Italy
Ospedale Sant' Eugenio
Rome, Italy, 00144
Macedonia, The Former Yugoslav Republic of
Clinical Center Skopje
Skopje, Macedonia, The Former Yugoslav Republic of, 91000
Leyenburg Ziekenhuis
's-Gravenhage, Netherlands, 2545 CH
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Hospital Escolar San Joao
Porto, Portugal, 4200
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
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OverallOfficial: Branimir Jaksic, MD, PhD University of Zagreb Medical School
Layout table for additonal information Identifier: NCT00017108    
Other Study ID Numbers: CDR0000068650
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: July 24, 2008
Last Verified: June 2004
Keywords provided by National Cancer Institute (NCI):
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
Additional relevant MeSH terms:
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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