Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia

August 18, 2015 updated by: French Study Group on Chronic Lymphoid Leukemia

Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma

Waldenström's macroglobulinaemia (WM) is a lymphoproliferative disorder characterized by a monoclonal IgM paraprotein and morphological evidence of lymphoplasmacytic lymphoma: the cells are IgM+, IgD+, CD19+ and CD20+ but usually CD5-, CD10- and CD23-. The treatment efficacy is difficult to assess because of the lack of clear diagnostic criteria , good response criteria, and of randomized trials.

The actual treatment is Chlorambucil, an alkylating agent. A purine analogue such as Fludarabine has proven its efficacy on 30 % to 80 % as first line therapy

This study is a phase II b open, prospective, international multicenter trial (England, Dr Johnson, Dr Catovsky, Australia: Dr Seymour) promoted by the French Cooperative Group on Chronic Lymphoid Leukemia in untreated WM, or closely related disorders ( Lymphoplasmacytic lymphoma or splenic marginal zone lymphoma). 366 patients must be included, among them 180 patients in France. Patients will be stratified according to the lymphoproliferative disorder.

The patients will receive Chlorambucil by oral route for 10 days every 28 days (12 cycles) (8 MG/M², 6 MG/M² if patient is more than 75 years old) or Fludarabine by oral route for 5 days every 28 days (6 cycles) (40MG/M², 30 MG/M² if patient is more than 75 years old).

The primary objective is to compare the efficacy (response rate) of Chlorambucil to Fludarabine in previously untreated patients. The secondary objectives are the duration of response, the improvement of hematological parameters, the toxicity, the quality of life, the event free survival and the overall survival.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

414

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

  • France
      • Paris, France, 75013
        • Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Established diagnosis of Waldenström macroglobulinemia (the 2nd Workshop on Waldenstrom's macroglobulinemia) or Lymphoplasmacytic lymphoma or Splenic Marginal Zone Lymphoma, needing a treatment

  • Life expectancy > 6 months
  • Creatinine < 200 µmol/l
  • SGPT and SGOT < 2x ULN
  • A negative direct Coombs test
  • Written informed consent

Exclusion Criteria:

  • Past chemotherapy/radiotherapy/immunotherapy prior to the study for Waldenström macroglobulinemia
  • Previous malignancy less than 5 years ago except carcinoma in situ of the cervix and non-melanoma skin cancer
  • Positive HIV serology
  • Active Hepatitis B or C
  • Lactation/pregnancy
  • Impossible good compliance with the study protocol
  • Active infection not controlled
  • Psychological condition hampering understanding of the study
  • Transformation into large B cell lymphoma
  • Peripheral neuropathy > grade II

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
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
Chlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months
Drug: Chlorambucil
Chlorambucil 8 mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months By oral route
Active Comparator: 2
Fludarabine
Drug: Fludarabine
Fludarabine 40 mg/m² (30 mg/m² if patient aged more than 75 years old) 5 days every 28 days during 6 cycles By oral route

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Patient overall response
Time Frame: At the end of treatment whether 6 or 12 months
At the end of treatment whether 6 or 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 60 months
60 months
Biological study
Time Frame: Whether 6 or 12 months
Whether 6 or 12 months
Quality of life
Time Frame: Whether 6 or 12 months
Whether 6 or 12 months
Response duration
Time Frame: 60 months
60 months
Treatment toxicity
Time Frame: 60 months
60 months
Event free survival
Time Frame: 60 months
60 months

Collaborators and Investigators

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

Sponsor

French Study Group on Chronic Lymphoid Leukemia

Collaborators

French Innovative Leukemia Organisation
Lymphoma Study Association
Département de Biostatistiques et Informatique Médicale DBIM

Investigators

  • Principal Investigator: Véronique LEBLOND, Professor, French Study Group on Chronic Lymphoid Leukemia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 2001

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

November 30, 2007

First Submitted That Met QC Criteria

November 30, 2007

First Posted (Estimate)

December 3, 2007

Study Record Updates

Last Update Posted (Estimate)

August 19, 2015

Last Update Submitted That Met QC Criteria

August 18, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WM1

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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