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

Waldenstrom's Disease Clinical Trial

— SérieProWM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05911802
• Other study ID #: FILObs_SérieProWM
• Status: Recruiting
• 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
• 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
• 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.

Related Conditions & MeSH terms

• Osteochondritis
• Waldenstrom's Disease

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