Study of Individuals and Families With Aberrations in DDX41 or Similar Cancer Predisposition Variants

NCT07019155 | Recruiting

• 2 other identifiers: 10002394002394-C
• Study Type: observational
• Target: 510
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Hereditary hematopoietic malignancy (HHM) syndromes are a group of inherited disorders that raises the risk of blood cancers. Many people with HHMs have changes in a gene (DDX41) that makes it more likely that they will develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or other cancers. This natural history study will explore the link between HHM syndromes and these diseases. Objective: To study the link between HHM and MDS/AML. Eligibility: People aged 1 month and older with HHM. Relatives with HHM are also needed. Design: Participants aged 3 years and older will have 1 initial clinic visit with the option to follow-up annually. They will undergo these procedures: They will have a physical exam with blood and urine tests. They may give samples of saliva, stool, nails, and skin. Their ability to do normal activities will be reviewed. Some may have a bone marrow biopsy: A tissue sample will be drawn from inside a bone. They may answer questions about their health and family medical history. Participants younger than 3 years, and those who cannot come to the clinic, will be contacted by phone or email. Their samples may be collected locally and sent to researchers. For participants who have changes in their DDX41 gene: Researchers will contact them or their primary care provider once a year for 10 years. Researchers will check on participants health and collect any new test results. Some may be asked to send new samples. Participants who do not have changes in their DDX41 gene may be contacted yearly, or less often, for 10 years. Some participants may be asked to return to the clinic if needed.

Conditions

Germline Mutation; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Keywords

DEAD-box helicase 41 (DDX41); germline mutations; MDS; AML; Germline Predisposition Syndromes; Hereditary Hematopoietic Malignancy; Cancer Predisposition

Outcome Measures

Primary Outcomes (1)

• To estimate the EFS in individuals with DEAD-box helicase 41 (DDX41) aberrations

  Describe the EFS separately for Cohort 1 and Cohort 2. Kaplan-Meier plots will be generated, five and 10-year EFS will be reported, along with 95% confidence intervals for each Cohort separately.

  Up to 10 years

Secondary Outcomes (2)

• To define the OS in individuals with DDX41 aberrations

  Up to 10 years

• To identify secondary commonly co-mutated somatic or germline variants as well as underrepresented mutations that may impact clinical presentation, disease severity, progression to malignancies.

  Up to 10 years

Study Arms (4)

Cohort 1

Participants with confirmed aberrations that affect the DDX41 gene, DDX41 RNA, or DDX41 protein and who have a history of MDS/MPN/AML diagnosis

Cohort 2

Participants with confirmed aberrations that affect the DDX41 gene, DDX41 RNA, or DDX41 protein and who do NOT have history of MDS/MPN/AML

Cohort 3

Participants with confirmed aberrations in another HHM variant

Cohort 4

Participants with confirmed absence of known HHM variants, and who have first or second degree relative with confirmed or suspected HHM variant(s) (control group)

Eligibility Criteria

• Age: 1 Month - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants with aberrations in DDX41 or other HHMs and relatives of individuals with aberrations in DDX41 or other HHMs.

You may qualify if:

• Age \> 1 month old.
• Participants with history of aberrations that affect the DDX41 gene, DDX41 RNA, or DDX41 protein (Cohorts 1-2)
• Participants with history of aberrations in another HHM variant (Cohort 3)
• Participants with history of absence of HHM variants, who have first or second degree relative with history of confirmed or suspected HHM variant(s) per participant report (Cohort 4).
• Participants must have an identified healthcare provider outside of NIH who manages participant care, and any diagnostic clinical findings provided by this study.
• Ability of participant or parent/guardian to understand and the willingness to sign a written consent document.

You may not qualify if:

• None.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Sung-Yun Pai, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca B Alexander

CONTACT

(240) 781-4037; rebecca.alexander@nih.gov

Sung-Yun Pai, M.D.

CONTACT

(240) 858-7284; sung-yun.pai@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2025
• First Posted: June 13, 2025
• Study Start: July 24, 2025
• Primary Completion (Estimated): June 15, 2035
• Study Completion (Estimated): June 15, 2035
• Last Updated: April 30, 2026

Record last verified: 2026-04-27

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
• Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.

Locations

US (1)