Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia

Splenic Marginal Zone Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00566332
• Other study ID #: WM1
• Status: Completed
• Phase: Phase 3
• First received: November 30, 2007
• Last updated: August 18, 2015
• Start date: June 2001
• Est. completion date: December 2014

Study information

• Verified date: August 2015
• Source: French Study Group on Chronic Lymphoid Leukemia
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 414
• Est. completion date: December 2014
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoplasmacytic Lymphoma
• Splenic Marginal Zone Lymphoma
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• Chlorambucil
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
• Fludarabine
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

Locations

Country	Name	City	State
France	Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital	Paris

Sponsors (4)

Lead Sponsor	Collaborator
French Study Group on Chronic Lymphoid Leukemia	Département de Biostatistiques et Informatique Médicale DBIM, Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS, Lymphoma Study Association

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient overall response		At the end of treatment whether 6 or 12 months	Yes
Secondary	Biological study		Whether 6 or 12 months	No
Secondary	Quality of life		Whether 6 or 12 months	No
Secondary	Response duration		60 months	Yes
Secondary	Treatment toxicity		60 months	Yes
Secondary	Event free survival		60 months	Yes
Secondary	Overall survival		60 months	Yes