Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia

Study Overview
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Brief Summary
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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.

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

Conditions
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Waldenström Macroglobulinemia, Lymphoplasmacytic Lymphoma, Splenic Marginal Zone Lymphoma

Intervention / Treatment
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* Drug: Chlorambucil
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Chlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months | Drug: Chlorambucil<br>* 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<br>|
| Active Comparator: 2<br>Fludarabine | Drug: Fludarabine<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenström Macroglobulinemia, Lymphoplasmacytic lymphoma, Splenic Marginal Zone Lymphoma, Fludarabine, Chlorambucil