Brief Title
Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia
Official Title
Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Patient overall response
Secondary Outcome
Biological study
Condition
Waldenström Macroglobulinemia
Intervention
Chlorambucil
Study Arms / Comparison Groups
1
Description: Chlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
414
Start Date
June 2001
Completion Date
December 2014
Primary Completion Date
September 2009
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Véronique LEBLOND, Professor, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT00566332
Organization ID
WM1
Responsible Party
Sponsor
Study Sponsor
French Study Group on Chronic Lymphoid Leukemia
Collaborators
Lymphoma Study Association
Study Sponsor
Véronique LEBLOND, Professor, Principal Investigator, French Study Group on Chronic Lymphoid Leukemia
Verification Date
August 2015