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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05911802
Other study ID # FILObs_SérieProWM
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date August 11, 2023
Est. completion date June 15, 2030

Study information

Verified date August 2023
Source French Innovative Leukemia Organisation
Contact n/a
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

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.


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


Recruitment information / eligibility

Status Recruiting
Enrollment 500
Est. completion date June 15, 2030
Est. primary completion date June 15, 2030
Accepts healthy volunteers
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Locations

Country Name City State
France AMIENS - CH Amiens Picardie Site Sud Amiens
France Angers Chu Angers
France Institut Bergonie Bordeaux
France Clermont-Ferrand - Chu Estaing Clermont-Ferrand
France Le Mans CH Le Mans
France LENS - GHT Artois Lens
France LIBOURNE - Hôpital Robert Boulin Libourne
France LILLE GHICL - Hôpital Saint Vincent de Paul Lille
France Institut Paoli Calmette Marseille
France APHP - Hôpital Pitié Salpêtrière - Hématologie Paris
France POITIERS - Hématologie et Thérapie Cellulaire Poitiers
France Reims Chu Reims
France Strasbourg - Icans Strasbourg
France Toulouse - IUCT Oncopole - Service d'Hématologie Toulouse
France VERSAILLES - Hôpital André Mignot Versailles

Sponsors (1)

Lead Sponsor Collaborator
French Innovative Leukemia Organisation

Country where clinical trial is conducted

France, 

References & Publications (1)

Royston P, Altman DG. External validation of a Cox prognostic model: principles and methods. BMC Med Res Methodol. 2013 Mar 6;13:33. doi: 10.1186/1471-2288-13-33. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Overall survival Percentage of living patients 5 years after WM diagnosis
Secondary Progression free survival percentage of living patients without disease progression 1 year after WM diagnosis
Secondary Tolerance to treatment percentage of patients discontinuing WM treatment due to toxicity 1 year after initiating WM treatment
See also
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Recruiting NCT03952052 - Detection of Recurrent Mutations in Waldenström's Disease N/A
Completed NCT03329950 - A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies Phase 1