Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia

French Study Group on Chronic Lymphoid Leukemia

Status and phase: Completed; Phase 3

Conditions: Waldenström Macroglobulinemia; Splenic Marginal Zone Lymphoma; Lymphoplasmacytic Lymphoma

Treatments: Drug: Chlorambucil; Drug: Fludarabine

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00566332

WM1

Details and patient eligibility

About

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.

Enrollment: 414 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

414 participants in 2 patient groups

1

Active Comparator group

Description:

Chlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months

Treatment:

Drug: Chlorambucil

2

Active Comparator group

Description:

Fludarabine

Treatment:

Drug: Fludarabine