Chlorambucil in Treating Patients With Advanced Chronic Lymphocytic Leukemia

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)

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.

Study Overview

Detailed Description

OBJECTIVES:

  • 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.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
      • Brussels, Belgium, 1070
        • Hopital Universitaire Erasme
      • Haine Saint Paul, Belgium, 7100
        • Hôpital de Jolimont
      • Olomouc, Czech Republic, 775 20
        • University Hospital - Olomouc
      • Kaposvar, Hungary, H-7400
        • County Hospital
      • Messina, Italy
        • Azienda Ospedaliera Papardo
      • Rome, Italy, 00144
        • Ospedale Sant' Eugenio
      • Skopje, Macedonia, The Former Yugoslav Republic of, 91000
        • Clinical Center Skopje
      • 's-Gravenhage, Netherlands, 2545 CH
        • Leyenburg Ziekenhuis
      • Amsterdam, Netherlands, 1091 HA
        • Onze Lieve Vrouwe Gasthuis
      • Leiden, Netherlands, 2300 CA
        • Leiden University Medical Center
      • Nijmegen, Netherlands, NL-6500 HB
        • University Medical Center Nijmegen
      • Porto, Portugal, 4200
        • Hospital Escolar San Joao

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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)

PATIENT CHARACTERISTICS:

Age:

  • 18 to 75

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

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

Renal:

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

Cardiovascular:

  • 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

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Prior steroid therapy for less than 2 weeks allowed

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Branimir Jaksic, MD, PhD, University of Zagreb Medical School

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2001

Study Registration Dates

First Submitted

June 6, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

July 24, 2008

Last Update Submitted That Met QC Criteria

July 23, 2008

Last Verified

June 1, 2004

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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