Registry of Relatives and Patients Carrying Pathogenic Germline DDX41 Variants and Emerging New Syndromes (preDDX)

The preDDX registry aims to study germline genetic predispositions to myeloid neoplasms, in particular those associated with pathogenic DDX41 variants and emerging syndromes.

Study Overview

• Status: Not yet recruiting
• Conditions: Myeloid Neoplasms (AML/MDS)

Detailed Description

The preDDX registry aims to study germline genetic predispositions to myeloid neoplasms, in particular those associated with pathogenic DDX41 variants and emerging syndromes.

It includes patients and, where applicable, their relatives, with prospective collection of clinical, biological and genetic data.

It is a Category 2 Research Involving the Human Person (RIPH2), based mainly on data from routine care, with no imposed therapeutic intervention. Additional procedures with minimal risks and constraints may be performed if necessary.

The data collected will help to better characterize these predispositions and their evolution in real-world practice.

• Study Type: Observational
• Enrollment (Estimated): 525

Contacts and Locations

• Study Contact: Name: Fatiha CHERMAT, PhD; Phone Number: + 33 1 71 20 70 59; Email: fatiha.chermat-ext@aphp.fr
• Study Contact Backup: Name: Marie SEBERT, Pr; Phone Number: + 33 1 71 20 70 18; Email: marie.sebert@aphp.fr

Study Locations

• France
  • Argenteuil, France, 95107
    • Centre Hospitalier Argenteuil
    • Contact: Benjamin PAPOULAR, MD; Phone Number: +33 1 34 23 20 16; Email: benjamin.papoular@ch-argenteuil.fr
    • Principal Investigator: Benjamin PAPOULAR, MD
  • Bobigny, France, 93000
    • Hôpital Avicenne
    • Contact: Ramy RAHME, MD; Phone Number: +33 1 48 95 70 71; Email: ramy.rahme@aphp.fr
    • Principal Investigator: Ramy RAHME, MD
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Bicêtre
    • Contact: Marie LE CANN, MD; Phone Number: +33 1 45 21 25 34; Email: marie.lecann@aphp.fr
    • Principal Investigator: Marie LE CANN, MD
  • Paris, France, 75012
    • Hôpital Saint-Antoine
    • Contact: Pierre HIRSCH, MD; Phone Number: +33 1 49 28 23 57; Email: pierre.hirsch@aphp.fr
    • Principal Investigator: Pierre HIRSCH, MD
  • Paris, France, 75014
    • Hôpital Cochin
    • Principal Investigator: Lise WILLEMS, MD
    • Contact: Lise WILLEMS, MD; Phone Number: +33 1 58 41 21 20; Email: lise.willems@aphp.fr
  • Paris, France, 75005
    • Institut Curie
    • Contact: Chrystelle COLAS, MD; Phone Number: +33 1 72 38 94 30; Email: chrystelle.colas@curie.fr
    • Principal Investigator: Chrystelle COLAS, MD
    • Principal Investigator: Léa VEYRUNE, MD
  • Paris, France, 75010
    • Hôpital Saint Louis
    • Contact: Marie SEBERT, MD, PhD; Phone Number: +33 1 71 20 70 18/19; Email: marie.sebert@aphp.fr
    • Principal Investigator: Marie SEBERT, MD, PhD
  • Villejuif, France, 94805
    • Institut Gustave Roussy
    • Contact: Jean baptiste MICOL, MD; Phone Number: +33 1 42 11 57 90; Email: Jeanbaptiste.MICOL@gustaveroussy.fr
    • Principal Investigator: Jean baptiste MICOL, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The registry includes adult patients carrying a germline variant associated with a predisposition to myeloid neoplasms and their biological relatives, where relevant.

Description

Inclusion Criteria:

• Male or female
• Age ≥ 18 years
• Presence of a germline variant (pathogenic, likely pathogenic or in a candidate gene)
• Followed in a participating center
• Able and willing to provide written informed consent

Exclusion Criteria:

• No identified or suspected genetic predisposition
• No consent

Study Plan

How is the study designed?

Design Details

• Observational Models: COHORT
• Time Perspectives: PROSPECTIVE

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Main cohort; Patients and carriers of pathogenic DDX41 variants: cohort dedicated to the study of patients and relatives carrying DDX41 variants.
Exploratory cohort; Cohort dedicated to the study of candidate genes and new predisposition syndromes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age- and sex-specific cumulative incidence of myeloid neoplasms in asymptomatic carriers of a germline DDX41 variant (Main cohort)	Hematological penetrance, estimated as the cumulative risk of developing a myeloid neoplasm (in particular MDS or AML) according to age and sex, using family-based methods that correct for ascertainment bias	From inclusion up to 5 years (end of registry)
Number of new hereditary syndromes predisposing to myeloid neoplasms identified and characterized (Exploratory cohort)	Identification and clinical, biological and genetic characterization of new germline predisposition syndromes, based on variants in candidate genes classified according to ACMG criteria	Through registry completion, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Factors associated with onset and progression of myeloid neoplasms in germline DDX41 variant carriers (Main cohort)	Association between clinical characteristics (age, sex, comorbidities), exposures, associated germline variants and somatic events, and the occurrence or progression of myeloid neoplasms, with death as a competing event.	From inclusion up to 5 years
Frequency of hematological and extra-hematological manifestations in germline DDX41 variant carriers (Main cohort)	Proportion of participants with each phenotype: myeloid neoplasms, extra-hematological manifestations and other associated entities	At inclusion and up to 5 years
Response to treatment and overall survival in patients with DDX41-associated MDS or AML Main cohort)	Response rates according to standard disease-specific response criteria, and overall survival	From inclusion up to 5 years
Penetrance of germline variants identified in candidate genes (Exploratory cohort)	Age-specific cumulative risk of myeloid neoplasms among carriers of variants in candidate genes	From inclusion up to 5 years
Clonal evolution in carriers of germline variants in candidate genes (Exploratory cohort)	Description of tumor evolution and trajectories: type and timing of acquired somatic and cytogenetic events and progression to MDS/AML	From inclusion up to 5 years
Proportion of candidate-gene variants with functional evidence of pathogenicity (Exploratory cohort)	Functional significance of variants assessed by biological analyses and functional assays	Through registry completion, up to 5 years

Collaborators and Investigators

• Sponsor: Groupe Francophone des Myelodysplasies
• Investigators: Principal Investigator: Marie SEBERT, Pr, Hôpital Saint Louis

Study record dates

Study Major Dates

• Study Start (Estimated): November 15, 2026
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): November 15, 2031

Study Registration Dates

• First Submitted: November 4, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 9, 2026

Study Record Updates

• Last Update Posted (Actual): November 9, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: AML; MDS; DDX41 variants
• Other Study ID Numbers: PreDDX Registry; 2026-A01030-51 (Registry Identifier: preDDX)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Sharing of pseudonymized individual data may be considered on reasoned request to the sponsor, subject to scientific review, GDPR compliance and applicable French regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No