NCT00566332

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
414

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 2001

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2001

Completed
6.5 years until next milestone

First Submitted

Initial submission to the registry

November 30, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 3, 2007

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2009

Completed
5.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

August 19, 2015

Status Verified

August 1, 2015

Enrollment Period

8.3 years

First QC Date

November 30, 2007

Last Update Submit

August 18, 2015

Conditions

Waldenström MacroglobulinemiaLymphoplasmacytic LymphomaSplenic Marginal Zone Lymphoma

Keywords

Waldenström MacroglobulinemiaLymphoplasmacytic lymphomaSplenic Marginal Zone LymphomaFludarabineChlorambucil

Outcome Measures

Primary Outcomes (1)

  • Patient overall response

    At the end of treatment whether 6 or 12 months

Secondary Outcomes (6)

  • 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

  • +1 more secondary outcomes

Study Arms (2)

1

ACTIVE COMPARATOR

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

Drug: Chlorambucil

2

ACTIVE COMPARATOR

Fludarabine

Drug: Fludarabine

Interventions

ChlorambucilDRUG

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

1
FludarabineDRUG

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

2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hôpital La Pitié-Salpêtrière. 47-83 Bd de l'hôpital

Paris, 75013, France

Location

Related Publications (2)

  • 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.

    PMID: 23233721DERIVED

  • 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.

    PMID: 23065509DERIVED

MeSH Terms

Conditions

Waldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal Zone

Interventions

Chlorambucilfludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Intervention Hierarchy (Ancestors)

Nitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic Chemicals

Study Officials

  • Véronique LEBLOND, Professor

    French Study Group on Chronic Lymphoid Leukemia

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 30, 2007

First Posted

December 3, 2007

Study Start

June 1, 2001

Primary Completion

September 1, 2009

Study Completion

December 1, 2014

Last Updated

August 19, 2015

Record last verified: 2015-08

Locations

FR(1)