Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia
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.
|Waldenström Macroglobulinemia Lymphoplasmacytic Lymphoma Splenic Marginal Zone Lymphoma||Drug: Chlorambucil Drug: Fludarabine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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|
- Patient overall response [ Time Frame: At the end of treatment whether 6 or 12 months ]
- Biological study [ Time Frame: Whether 6 or 12 months ]
- Quality of life [ Time Frame: Whether 6 or 12 months ]
- Response duration [ Time Frame: 60 months ]
- Treatment toxicity [ Time Frame: 60 months ]
- Event free survival [ Time Frame: 60 months ]
- Overall survival [ Time Frame: 60 months ]
|Study Start Date:||June 2001|
|Study Completion Date:||December 2014|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
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
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00566332
|Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital|
|Paris, France, 75013|
|Principal Investigator:||Véronique LEBLOND, Professor||French Study Group on Chronic Lymphoid Leukemia|