Lymphoplasmacytic Lymphoma, Splenic Marginal Zone Lymphoma, Waldenström Macroglobulinemia
Conditions
Keywords
Waldenström Macroglobulinemia, Lymphoplasmacytic lymphoma, Splenic Marginal Zone Lymphoma, Fludarabine, Chlorambucil
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.
Interventions
DRUGChlorambucil
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
DRUGFludarabine
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
Sponsors
Lymphoma Study Association
French Innovative Leukemia Organisation
Département de Biostatistiques et Informatique Médicale DBIM
French Study Group on Chronic Lymphoid Leukemia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patient overall response | At the end of treatment whether 6 or 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Quality of life | Whether 6 or 12 months |
| Response duration | 60 months |
| Biological study | Whether 6 or 12 months |
| Event free survival | 60 months |
| Overall survival | 60 months |
| Treatment toxicity | 60 months |
Countries
France
Outcome results
None listed