Clinical trial NCT00566332: Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia
Official title: Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Waldenström Macroglobulinemia
Lymphoplasmacytic Lymphoma
Splenic Marginal Zone Lymphoma
Keywords: Waldenström Macroglobulinemia
Lymphoplasmacytic lymphoma
Splenic Marginal Zone Lymphoma
Fludarabine
Chlorambucil
Lead sponsor: French Study Group on Chronic Lymphoid Leukemia
Sponsor class: NETWORK
Collaborators: name: Lymphoma Study Association
name: French Innovative Leukemia Organisation
name: Département de Biostatistiques et Informatique Médicale DBIM
First posted: 2007-12-03
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Patient overall response
timeFrame: At the end of treatment whether 6 or 12 months
Secondary outcomes:
measure: Biological study
timeFrame: Whether 6 or 12 months
measure: Quality of life
timeFrame: Whether 6 or 12 months
measure: Response duration
timeFrame: 60 months
measure: Treatment toxicity
timeFrame: 60 months
measure: Event free survival
timeFrame: 60 months
measure: Overall survival
timeFrame: 60 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital
Study officials:
affiliation: French Study Group on Chronic Lymphoid Leukemia
name: Véronique LEBLOND, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi: 10.1200/JCO.2012.44.7920. Epub 2012 Dec 10.
citation: Nguyen-Khac F, Lambert J, Chapiro E, Grelier A, Mould S, Barin C, Daudignon A, Gachard N, Struski S, Henry C, Penther D, Mossafa H, Andrieux J, Eclache V, Bilhou-Nabera C, Luquet I, Terre C, Baranger L, Mugneret F, Chiesa J, Mozziconacci MJ, Callet-Bauchu E, Veronese L, Blons H, Owen R, Lejeune J, Chevret S, Merle-Beral H, Leblondon V; Groupe Francais d'Etude de la Leucemie Lymphoide Chronique et Maladie de Waldenstrom (GFCLL/MW); Groupe Ouest-Est d'etude des Leucemie Aigues et Autres Maladies du Sang (GOELAMS); Groupe d'Etude des Lymphomes de l'Adulte (GELA). Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia. Haematologica. 2013 Apr;98(4):649-54. doi: 10.3324/haematol.2012.070458. Epub 2012 Oct 12.