We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia

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.
ClinicalTrials.gov Identifier: NCT00566332
Recruitment Status : Completed
First Posted : December 3, 2007
Last Update Posted : August 19, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Waldenström Macroglobulinemia Lymphoplasmacytic Lymphoma Splenic Marginal Zone Lymphoma Drug: Chlorambucil Drug: Fludarabine Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 414 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma
Study Start Date : June 2001
Primary Completion Date : September 2009
Study Completion Date : December 2014

Arms and Interventions

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
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

Outcome Measures

Primary Outcome Measures :
  1. Patient overall response [ Time Frame: At the end of treatment whether 6 or 12 months ]

Secondary Outcome Measures :
  1. Biological study [ Time Frame: Whether 6 or 12 months ]
  2. Quality of life [ Time Frame: Whether 6 or 12 months ]
  3. Response duration [ Time Frame: 60 months ]
  4. Treatment toxicity [ Time Frame: 60 months ]
  5. Event free survival [ Time Frame: 60 months ]
  6. Overall survival [ Time Frame: 60 months ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT00566332

Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital
Paris, France, 75013
Sponsors and Collaborators
French Study Group on Chronic Lymphoid Leukemia
Lymphoma Study Association
French Innovative Leukemia Organisation
Département de Biostatistiques et Informatique Médicale DBIM
Principal Investigator: Véronique LEBLOND, Professor French Study Group on Chronic Lymphoid Leukemia
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French Study Group on Chronic Lymphoid Leukemia
ClinicalTrials.gov Identifier: NCT00566332     History of Changes
Other Study ID Numbers: WM1
First Posted: December 3, 2007    Key Record Dates
Last Update Posted: August 19, 2015
Last Verified: August 2015

Keywords provided by French Study Group on Chronic Lymphoid Leukemia:
Waldenström Macroglobulinemia
Lymphoplasmacytic lymphoma
Splenic Marginal Zone Lymphoma

Additional relevant MeSH terms:
Lymphoma, B-Cell, Marginal Zone
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs