Understanding the risks of blood disorders in families with DDX41 gene mutations

Study of Families With an Hemopathies Predisposition Related to the DDX41 Gene.

This study is trying to see if people with a specific gene mutation in their family are at higher risk for blood disorders like leukemia and how this information can help their family members.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 910 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institut Claudius Regaud (Academic / other)
• Locations: 5 sites (Bordeaux and 4 other locations)
• Trial ID: NCT06022016 on ClinicalTrials.gov

What this trial studies

This multicenter pilot study aims to identify the phenotype of individuals carrying a familial DDX41 mutation and assess their risk of developing hematological diseases such as myelodysplastic syndrome and acute myeloid leukemia. The study will involve two stages: first, the inclusion of index cases through oncogenetic consultations and health questionnaires, followed by outreach to family members to determine their carrier status via salivary tests. The goal is to gather data that will inform oncogenetic recommendations for mutation carriers.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a personal history of blood disorders or confirmed DDX41 mutations.

Not a fit: Patients without a DDX41 mutation or those without a personal history of hematological conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the risks associated with DDX41 mutations, leading to better management and preventive strategies for affected families.

How similar studies have performed: While the specific approach of this study is novel, similar studies have shown promise in understanding genetic predispositions to hematological diseases.

Eligibility criteria

Index cases:

Inclusion Criteria:

1. Women or man aged ≥ 18 years old.
2. Personal history(s) of hemopathy or patient with hemopathy at the time of inclusion.
3. Patient with a tumor mutation of DDX41 with an allelic frequency (AF) ≥ 30% (with total depth of nucleotide position \>300x: provide tumor molecular analysis report).

   Special case of inclusion of deceased index cases: the DDX41 tumor mutation of interest must be accompanied by another somatic DDX41 mutation (the most frequent being p.R525H).

   Or patient known to be a constitutional carrier of a DDX41 mutation confirmed after oncogenetic consultation (in this case, provide constitutional analysis report).
4. Patient (or beneficiary) agreeing to release results of oncogenetic report.
5. Patient (or beneficiary) agrees to communicate the contact details of his relatives and that they may be contacted by mail to participate in the LUCID study.
6. Patient affiliated to a Social Health Insurance in France.
7. Patient able to participate and willing to give informed consent prior performance of any study-related procedures.

Exclusion Criteria:

1. No history of hemopathy or no current hemopathy.
2. Patient (or beneficiary) unable to complete questionnaire for social or psychological reasons.
3. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

Related cases (Family member):

Inclusion Criteria:

1. Women or man aged ≥ 18 years old.
2. Related to an index case included in the LUCID study.
3. Agreeing to carry out a scientific salivary test for the constitutional research of the DDX41 mutation.
4. Patient affiliated to a Social Health Insurance in France.
5. Patient able to participate and willing to give informed consent prior performance of any study-related procedures.

Exclusion Criteria:

1. Not applicable from version 2 of the protocol. Related in the 4th or 5th degree to an index case included in the LUCID study.
2. Person already identified as an index case in the LUCID study.
3. Person unable to complete questionnaire for social or psychological reasons.
4. Person who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

Where this trial is running

Bordeaux and 4 other locations

• Chu de Bordeaux — Bordeaux, France (Recruiting)
• Chu de Limoges — Limoges, France (Recruiting)
• Institut Paoli-Calmettes — Marseille, France (Recruiting)
• Chu de Montpellier — Montpellier, France (Recruiting)
• Iuct-O — Toulouse, France (Recruiting)

Study contacts

• Study coordinator: Pierre VANDE PERRE

Conditions DDX41 Gene Mutation; GermlIne DDX41 mutation; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Idiopathic Cytopenia; LeUkemia