Individuals and families with DDX41 or similar inherited blood cancer risk variants
Longitudinal Study of Individuals and Families With Aberrations in DDX41 or Similar Cancer Predisposition Variants
We will follow people and their family members who have DDX41 or other inherited blood cancer risk variants to see how often and when they develop MDS or AML and related health changes.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 510 (estimated) |
| Ages | 1 Month to 120 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT07019155 on ClinicalTrials.gov |
What this trial studies
This is a natural history observational study enrolling people (age ≥1 month) with germline DDX41 changes, other hereditary hematopoietic malignancy (HHM) gene variants, or relatives of affected individuals. Participants aged 3 and older will have an initial clinic visit with optional annual follow-ups and routine assessments including physical exam, blood and urine testing, and reviews of daily functioning. Optional biospecimen collection may include saliva, stool, nails, skin, and in some cases bone marrow sampling to document molecular and clinical changes over time. The goal is to define the clinical course, timing of disease onset, and associated molecular events to improve identification and management of HHM-related MDS/AML.
Who should consider this trial
Good fit: Ideal candidates are people aged 1 month or older with a confirmed or suspected germline DDX41 variant, other HHM gene variants, or first- or second-degree relatives of someone with a confirmed or suspected HHM variant.
Not a fit: People without HHM variants and without a close relative carrying such variants are unlikely to gain direct clinical benefit from this observational natural history study.
Why it matters
Potential benefit: If successful, the study could improve early detection, genetic counseling, and clinical care plans for people with DDX41 and related hereditary variants.
How similar studies have performed: Previous research has identified DDX41 as a recurrent germline predisposition to myeloid neoplasms and shown that associated cancers often respond to standard chemotherapy, but comprehensive long-term natural history data remain limited.
Eligibility criteria
Show full inclusion / exclusion criteria
* INCLUSION CRITERIA: * Age \> 1 month old. * Participants with history of aberrations that affect the DDX41 gene, DDX41 RNA, or DDX41 protein (Cohorts 1-2) OR Participants with history of aberrations in another HHM variant (Cohort 3) OR 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. EXCLUSION CRITERIA: None.
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Sung-Yun Pai, M.D. — National Cancer Institute (NCI)
- Study coordinator: Rebecca B Alexander
- Email: rebecca.alexander@nih.gov
- Phone: (240) 781-4037
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.