Waldenstrom's DiseaseDigiWALNCT03952052
Detection of Recurrent Mutations in Waldenström's Disease
A study testing Determination of mutation in people with Waldenstrom's Disease, run by Centre Henri Becquerel at 1 site in France.
Trial summary
Waldenström's disease (WM) is a rare, low-grade lymphoid hematopathy, accounting for 1 to 2% of malignant hematopathies and mainly affecting the elderly. This disease is characterized by lymphoplasmocyte cells infiltration into the bone marrow and by the production of a monoclonal IgM protein in the serum. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom's Disease
- What is being tested?
- Determination of mutation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- 14 Jan 2019to 5 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Over 18 years of age
- recently diagnosed for Waldenström's disease
- not yet treated for Waldenström's disease
Who cannot join
- Pregnancy or breast feeding
- HBV or HBC positive
- HIV positive
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Detection by Digital PCR and Next Generation Sequencing of Recurrent Mutations in Waldenström's Disease and Study of Their Distribution in the Different Biological Compartments
Waldenström's disease (WM) is a rare, low-grade lymphoid hematopathy, accounting for 1 to 2% of malignant hematopathies and mainly affecting the elderly. This disease is characterized by lymphoplasmocyte cells infiltration into the bone marrow and by the production of a monoclonal IgM protein in the serum. This disease is accompanied by clinical manifestations of hepato-splenomegaly, signs of hyperviscosity, peripheral neuropathies and biological signs with the presence of cytopenias and cryoglobulinemia. Some forms present node or splenic involvement. While the asymptomatic form maintains overall survival close to that of the healthy subject, the symptomatic form is subject to frequent relapses and remains incurable.
Current recommendations for the diagnosis and monitoring of this disease are based on protein electrophoresis from a blood sample to quantify monoclonal IgM production and a myelogram or bone marrow biopsy showing medullary infiltration by lymphoplasmocytic cells. However, protein electrophoresis is an imprecise examination since it does not quantify tumour B lymphocytes and has limitations, particularly in the case of poorly secreting forms.
Read more
More than 90% of Waldenström cases have the L265P mutation of the MYD88 gene. Although this mutation is not found only in these diseases, it can help in the diagnosis. Other mutations are also present in this pathology. These mutations can define prognostic factors or possibly make it possible to identify therapeutic targets.
The development of new technologies makes it possible, on the one hand, to follow the L265P mutation of MYD88 over time as a marker of response to treatment and, on the other hand, to define these prognostic markers or therapeutic targets.
This study will first determine the best method for monitoring the mutation of MYD88. In a second step, the investigators will evaluate the best type of sampling and in particular whether this mutation is present in the blood in order to limit the invasive procedures such as bone marrow sampling can be limited. Finally, the investigators will evaluate the prognostic
Read the detailed description
The L265P mutation of MYD88 appears as an early oncogenic event in the occurrence of Waldenström disease and may already be present at the Monoclonal Gammapathy of Undetermined Signification (MGUS) to IgM stage suggesting a continuum between the two stages of the disease. The determination of IgM as a marker of the disease has limits since it does not allow direct quantification of the clonal population and is taken failing this in the case of poorly secreting forms. Monitoring the L265P mutation of MYD88 as a marker of minimal residual disease therefore appears to be a biomarker of major interest in these diseases. The kinetics of this marker particularly during treatment could allow to modify the therapeutic management of patients at an early stage and to assess the risk of resistance to treatment.
Several published studies show the interest of monitoring the L265P mutation of MYD88 in MW in particular by quantification of the mutation by allele-specific PCR. The detection limit studied was 0.1%. The recent development of new techniques and in particular digital PCR makes it possible to obtain lower detection thresholds that could be more compatible with the notion of minimal residual disease monitoring.
The originality of this study is based on the comparison of the quantification of the MYD88 L265P mutation in all affected biological compartments (blood, plasma, bone marrow or CD19+ cells) but especially in the monitoring of the mutation at two points of minimal residual disease (mid-treatment and end of treatment).
One of the parts of the project is the study of the allelic frequency of the L265P mutation of the MYD88 gene in circulating tumor DNA (ctDNA). It has been shown in many pathologies and in particular in other B lymphocytic hematologies such as Hodgkin's lymphoma or diffuse large cell B lymphoma, that mutations present at the tumor level could be found in circulating tumor DNA. Analysis of free tumor DNA circulating in patients' plasma can therefore be used to characterize the disease at the molecular level with a less invasive sample than myelogram or bone marrow biopsies. The search for other associated mutations also reinforces the originality of the project. These combined data must be able to lead to changes in the clinical management of patients.
In this study, the allele frequency of the L265P mutation of MYD88 will be compared . by 3 different techniques: specific allele PCR, digital PCR and new generation sequencing. In this way, investigators will evaluate the technique that has the best sensitivity and specificity to be used as a marker for residual disease. These data will be compared to the reference technique, protein electrophoresis. This evaluation will be conducted in total mononuclear cells, DNAct, marrow and CD19+ sorted cells. Then, the investigators will follow the kinetics of this mutation during the treatment at two points : mid-treatment and end of treatment.
Characterization of the mutation profile of these tumors allows prognostic factors to be defined and may identify potential new therapeutic targets. This study will be realised by new generation sequencing. Some of genes with mutations involved in treatment resistance will be studied such as CXCR4. The mutations of CXCR4 are involved in the resistance to ibrutinib. ARID1A mutations are also found in 20% of cases as well as TP53, KMT2D, CD79B, MYBBP1A mutations.
- Conditions
- Waldenstrom's Disease
- Being tested
- Determination of mutation
- Keywords
- MRD, Mutation, Next Generation sequencing, Digital Polymeras Chain Reaction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Determination of mutationOther
Recurrent mutation determination by digital PCR and next generation sequencing
| Study group | Role | What they receive |
|---|---|---|
| Patient enrolled | Other | Recurrent mutations determination Receives: Other: Determination of mutation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of MYD88 L265P mutation
Comparison of level of MYD88L265P mutationin different biological compartment c.
Measured: one year
Secondary outcomes (2)
Allelic frequency of L265P mutation of MYD 88 gene
Comparison of allelic frequency determined by three different techniques (next generation sequencing, digital PCR and specific allele PCR)
Measured: one year
Kinetics of mutation
determination of the kinetics of mutation
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start14 Jan 2019
- Primary completion5 Dec 2022
- Study completion5 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenstrom's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Henri Becquerel
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pascaline Etancelin, Principal investigator, Centre Henri Becquerel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03952052
- Sponsor's protocol ID
- CHB 18.06
- Acronym
- DigiWAL
- Status last verified
- Dec 2025
- First submitted
- 7 May 2019
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection by Digital PCR and Next Generation Sequencing of Recurrent Mutations in Waldenström's Disease and Study of Their Distribution in the Different Biological Compartments
- ClinicalTrials.gov ID
- NCT03952052
- Acronym / sponsor ID
- DigiWAL / CHB 18.06
- Conditions
- Waldenstrom's Disease
- Keywords
- MRD, Mutation, Next Generation sequencing, Digital Polymeras Chain Reaction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Centre Henri BecquerelUniversity, hospital or other
- Study start
- 14 Jan 2019 (actual)
- Primary completion
- 5 Dec 2022 (actual)
- Study completion
- 5 Dec 2022 (actual)
- First posted
- 16 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Waldenström's disease (WM) is a rare, low-grade lymphoid hematopathy, accounting for 1 to 2% of malignant hematopathies and mainly affecting the elderly. This disease is characterized by lymphoplasmocyte cells infiltration into the bone marrow and by the production of a monoclonal IgM protein in the serum. This disease is accompanied by clinical manifestations of hepato-splenomegaly, signs of hyperviscosity, peripheral neuropathies and biological signs with the presence of cytopenias and cryoglobulinemia. Some forms present node or splenic involvement. While the asymptomatic form maintains overall survival close to that of the healthy subject, the symptomatic form is subject to frequent relapses and remains incurable.
Current recommendations for the diagnosis and monitoring of this disease are based on protein electrophoresis from a blood sample to quantify monoclonal IgM production and a myelogram or bone marrow biopsy showing medullary infiltration by lymphoplasmocytic cells. However, protein electrophoresis is an imprecise examination since it does not quantify tumour B lymphocytes and has limitations, particularly in the case of poorly secreting forms.
More than 90% of Waldenström cases have the L265P mutation of the MYD88 gene. Although this mutation is not found only in these diseases, it can help in the diagnosis. Other mutations are also present in this pathology. These mutations can define prognostic factors or possibly make it possible to identify therapeutic targets.
The development of new technologies makes it possible, on the one hand, to follow the L265P mutation of MYD88 over time as a marker of response to treatment and, on the other hand, to define these prognostic markers or therapeutic targets.
This study will first determine the best method for monitoring the mutation of MYD88. In a second step, the investigators will evaluate the best type of sampling and in particular whether this mutation is present in the blood in order to limit the invasive procedures such as bone marrow sampling can be limited. Finally, the investigators will evaluate the prognostic
Detailed description
The L265P mutation of MYD88 appears as an early oncogenic event in the occurrence of Waldenström disease and may already be present at the Monoclonal Gammapathy of Undetermined Signification (MGUS) to IgM stage suggesting a continuum between the two stages of the disease. The determination of IgM as a marker of the disease has limits since it does not allow direct quantification of the clonal population and is taken failing this in the case of poorly secreting forms. Monitoring the L265P mutation of MYD88 as a marker of minimal residual disease therefore appears to be a biomarker of major interest in these diseases. The kinetics of this marker particularly during treatment could allow to modify the therapeutic management of patients at an early stage and to assess the risk of resistance to treatment.
Several published studies show the interest of monitoring the L265P mutation of MYD88 in MW in particular by quantification of the mutation by allele-specific PCR. The detection limit studied was 0.1%. The recent development of new techniques and in particular digital PCR makes it possible to obtain lower detection thresholds that could be more compatible with the notion of minimal residual disease monitoring.
The originality of this study is based on the comparison of the quantification of the MYD88 L265P mutation in all affected biological compartments (blood, plasma, bone marrow or CD19+ cells) but especially in the monitoring of the mutation at two points of minimal residual disease (mid-treatment and end of treatment).
One of the parts of the project is the study of the allelic frequency of the L265P mutation of the MYD88 gene in circulating tumor DNA (ctDNA). It has been shown in many pathologies and in particular in other B lymphocytic hematologies such as Hodgkin's lymphoma or diffuse large cell B lymphoma, that mutations present at the tumor level could be found in circulating tumor DNA. Analysis of free tumor DNA circulating in patients' plasma can therefore be used to characterize the disease at the molecular level with a less invasive sample than myelogram or bone marrow biopsies. The search for other associated mutations also reinforces the originality of the project. These combined data must be able to lead to changes in the clinical management of patients.
In this study, the allele frequency of the L265P mutation of MYD88 will be compared . by 3 different techniques: specific allele PCR, digital PCR and new generation sequencing. In this way, investigators will evaluate the technique that has the best sensitivity and specificity to be used as a marker for residual disease. These data will be compared to the reference technique, protein electrophoresis. This evaluation will be conducted in total mononuclear cells, DNAct, marrow and CD19+ sorted cells. Then, the investigators will follow the kinetics of this mutation during the treatment at two points : mid-treatment and end of treatment.
Characterization of the mutation profile of these tumors allows prognostic factors to be defined and may identify potential new therapeutic targets. This study will be realised by new generation sequencing. Some of genes with mutations involved in treatment resistance will be studied such as CXCR4. The mutations of CXCR4 are involved in the resistance to ibrutinib. ARID1A mutations are also found in 20% of cases as well as TP53, KMT2D, CD79B, MYBBP1A mutations.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patient enrolled | Other | Other: Determination of mutationRecurrent mutations determination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Over 18 years of age
- recently diagnosed for Waldenström's disease
- not yet treated for Waldenström's disease
Key exclusion criteria (3 listed)
- Pregnancy or breast feeding
- HBV or HBC positive
- HIV positive
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Determination of mutationRecurrent mutation determination by digital PCR and next generation sequencing | Other | Patient enrolled |
Primary outcome
Quantification of MYD88 L265P mutation
Time frame: one year
Comparison of level of MYD88L265P mutationin different biological compartment c.
2 secondary outcomes
Allelic frequency of L265P mutation of MYD 88 gene
Time frame: one year
Kinetics of mutation
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
- Individual participant dataSharing planned: No
Related trials for Waldenstrom's Disease
RecruitingPhase 2
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Teclistamab In Waldenstrom's Macroglobulinemia
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Evaluation of Iopofosine I 131 vs. R-CD in WM Patients
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascaline Etancelin principal investigator
Centre Henri Becquerel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Determination of mutation in people with Waldenstrom's Disease, run by Centre Henri Becquerel at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of MYD88 L265P mutation (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026.