Prognostic Analyses on a Validation Series of Patients With Waldenström's Disease (SérieProWM)

November 21, 2025 updated by: French Innovative Leukemia Organisation

Prognostic Analyses on a Validation Series of Patients With Waldenström's Disease: Validation of International Prognostic Indexes, Evaluation of Progression-free Survival as a Surrogate Endpoint for Overall Survival. A FILO Study.

Waldenström's macroglobulinemia (WM) is defined by the association of bone marrow lymphoplasmocytic infiltration and monoclonal immunoglobulin M (IgM). A mutation in the MYD88 gene is found in up to 90% of patients, and a mutation in the CXCR4 gene in approximately one third of patients. Treatment should be initiated in cases of cytopenia, bulky disease or when the physicochemical or immunological properties of IgM explain the occurrence of amyloidosis, cryoglobulin, neurological manifestations, or hyperviscosity syndrome (due to the presence of a large amount of IgM). However, approximately 30% of patients are diagnosed without any symptom and therefore they do not meet the criteria for initiating treatment.

At the time of initiation of the first treatment, the prognosis is usually estimated with the International Prognostic Index (IPSSWM) which is based on five variables: age, platelet count, haemoglobin concentrations, β2-microglobulin and monoclonal component concentration. Serum albumin and lactate dehydrogénase (LDH) levels also retain a prognostic role and these two characteristics have been incorporated in a proposal for a revision of this index.

Improving prognostic assessment at the time of the first treatment initiation and taking into account the prognostic impact of events occurring in the course of evolution, should improve the strength of treatment decision at the time of initial treatment and during the follow-up. It should also help to design clinical trial for fast and effective evaluation of new treatments. Our work should also help to adjust clinical monitoring of asymptomatic patients.

Prospective and retrospective multicenter prognostic study with a descriptive objective, associated with a biological collection appropriately annotated and stored. A retrospective series including 470 patients with symptomatic WM is already available. The follow-up of these patients will be updated and an additional series of 250 symptomatic patients will be prospectively enrolled. 250 asymptomatic patients will be also enrolled.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Waldenström's macroglobulinemia (WM) is defined by the association of bone marrow lymphoplasmocytic infiltration and monoclonal immunoglobulin M (IgM). A mutation in the MYD88 gene is found in up to 90% of patients, and a mutation in the CXCR4 gene in approximately one third of patients. Treatment should be initiated in cases of cytopenia, bulky disease or when the physicochemical or immunological properties of IgM explain the occurrence of amyloidosis, cryoglobulin, neurological manifestations, or hyperviscosity syndrome (due to the presence of a large amount of IgM). However, approximately 30% of patients are diagnosed without any symptom and therefore they do not meet the criteria for initiating treatment.

The prognosis of asymptomatic patients can be estimated with a prognostic index based on serum albumin, β2-microglobulin, the monoclonal component concentration and the bone marrow infiltration. Prognostic assessment of these patients could be improved by taking into account prior the free light chain concentrations and the molecular characteristics of the disease.

At the time of initiation of the first treatment, the prognosis is usually estimated with the International Prognostic Index (IPSSWM) which is based on five variables: age, platelet count, haemoglobin concentrations, β2-microglobulin and monoclonal component concentration. Serum albumin and LDH levels also retain a prognostic role and these two characteristics have been incorporated in a proposal for a revision of this index.

Thus improving prognostic assessment in patients with WM may rest on the following strategies:

  • Modifying the variables to be considered before treatment initiation, particularly by considering albumin and lactate dehydrogenase concentrations or molecular characteristics of the disease in symptomatic patients, free-light chain concentration in asymptomatic patients and molecular abnormalities in both categories of patients.
  • Evaluating the prognostic impact of events occurring during the course of treatment, such as response or progression in symptomatic patients.

Improving prognostic assessment at the time of the first treatment initiation and taking into account the prognostic impact of events occurring in the course of evolution, should improve the strength of treatment decision at the time of initial treatment and during the follow-up. It should also help to design clinical trial for fast and effective evaluation of new treatments. Our work should also help to adjust clinical monitoring of asymptomatic patients.

Two large subgroups of patients properly included with validated information and updated follow-up will be considered, namely: symptomatic and asymptomatic patients. This project is based on the assumption that it should be possible for each of these two cohorts to:

  1. validate a new prognostic system and compare its performance with previous systems
  2. to participate in a large international study of the validity of a surrogate endpoint of survival after initiation of the 1st treatment

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
      • Angers, France, 49933
      • Bordeaux, France, 33076
      • Clermont-Ferrand, France, 63000
      • Le Mans, France
      • Lens, France, 62300
        • Not yet recruiting
        • LENS - GHT Artois
        • Contact:
      • Libourne, France, 33505
      • Lille, France, 59000
        • Recruiting
        • LILLE GHICL - Hôpital Saint Vincent de Paul
        • Contact:
      • Marseille, France, 130009
        • Not yet recruiting
        • Institut Paoli Calmette
        • Contact:
      • Paris, France, 75651
        • Not yet recruiting
        • APHP - Hôpital Pitié Salpêtrière - Hématologie
        • Contact:
      • Poitiers, France, 86021
        • Not yet recruiting
        • POITIERS - Hématologie et Thérapie Cellulaire
        • Contact:
      • Reims, France, 51092
      • Strasbourg, France, 67033
      • Toulouse, France, 31059
      • Versailles, France
        • Not yet recruiting
        • VERSAILLES - Hôpital André Mignot
        • Contact:
          • Fatiha MERABET, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

250 symptomatic patients and 250 asymptomatic patients will be prospectively enrolled

Description

Inclusion Criteria:

  • Patient with WM, fulfilling the diagnostic criteria defined at the 2nd Workshop on WM.
  • Patient in whom follow-up is available until at least 01/01/2020. Each participating center should not enroll more 10% of patients lost to follow-up.
  • Patient for whom a minimum annual follow-up is planned until 2024.
  • Having given their consent for this study

Exclusion Criteria:

  • Patient with other chronic lymphoid malignancy. Special attention will be paid to exclude other lymphoplasmacytic proliferations, especially marginal zone lymphoma.
  • Patient with histological transformation in a diffuse large B-cell lymphoma or any other lymphoma at the time of the initiation of the 1st treatment.
  • No consent for this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
symptomatic WM
WM patients with symptom(s) : cytopenia, bulky disease or when the physicochemical or immunological properties of IgM explain the occurrence of amyloidosis, cryoglobulin, neurological manifestations, or hyperviscosity syndrome (due to the presence of a large amount of IgM)
asymptomatic WM
WM patients without any symptom

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 5 years after WM diagnosis
Percentage of living patients
5 years after WM diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 1 year after WM diagnosis
percentage of living patients without disease progression
1 year after WM diagnosis
Tolerance to treatment
Time Frame: 1 year after initiating WM treatment
percentage of patients discontinuing WM treatment due to toxicity
1 year after initiating WM treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

French Innovative Leukemia Organisation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 11, 2023

Primary Completion (Estimated)

June 15, 2030

Study Completion (Estimated)

June 15, 2030

Study Registration Dates

First Submitted

June 12, 2023

First Submitted That Met QC Criteria

June 12, 2023

First Posted (Actual)

June 22, 2023

Study Record Updates

Last Update Posted (Actual)

November 26, 2025

Last Update Submitted That Met QC Criteria

November 21, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FILObs_SérieProWM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Specific or all individual participant data sets would be probably shared with the European ECWM Group. For example, data on use of BTKi ( Bruton tyrosine kinases inhibitors) in this population

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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