Inherited Hematological DiseasesNCT03854318
Longitudinal Studies of Patient With FPDMM
An observational study of Inherited Hematological Diseases and Rare Diseases, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Background: Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Read more about this study
- Who is it for?
- Ages 1 day to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Inherited Hematological Diseases, Rare Diseases, FPDMM
- How many people
- 1,000 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2019to 31 Dec 2099
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 1 day to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients (and direct family members of patients) enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation.
Who may be able to join
- Patients enrolled in this protocol will have been referred with a known or suspected variant in the RUNX1 gene. Patients with suspected RUNX1 variants are those with clinical features of FPD but who have not been tested for RUNX1, or who were negative on standard testing. The Principal Investigator, along with consulting specialists, will review the medical records of prospective patients and offer enrollment based upon the potential to help the individual, to learn from the patient, or to initiate clinical or basic research suggested by the patient's workup. Persons interested in participation may be given a screening questionnaire to determine eligibility. The questions about hematologic manifestations in the screening questionnaire are important to help us determine if RUNX1 variants are likely to be pathogenic, or if there is a high clinical suspicion of RUNX1 (abnormal platelets, bleeding, bruising, leukemia etc.). Unaffected family members may be asked to enroll in the study to provide specimens (saliva, blood, skin) for genetic testing, next-generation sequencing, and other related studies. Enrolled subjects can be any sex and any age. There are no upper or lower age restrictions on this study.
Who cannot join
- There are no exclusionary criteria.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Longitudinal Studies of Patients and Families With Familial Platelet Disorders With Associated Myeloid Malignancy (FPDMM) Caused by RUNX1 Germline Variants or FPDMM-Like Conditions
Background:
Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 variants and FPD.
Read more
Objective:
To learn more about FPD in people with RUNX1 variants to lead to better diagnosis, monitoring, and treatment.
Eligibility:
People any age with a suspected or confirmed RUNX1 variant
People who have a family member with the variant
Design:
All participants will be screened with a phone call and a blood, saliva, or cheek cell sample.
Participants with a suspected or confirmed variant will have 1 visit. It will last about 2 days. They will then have visits at least once a year.
Visits will include:
- Medical history and physical exam
- Blood tests or saliva sample
- Possible skin biopsy: A small piece of the participant s skin will be removed.
- Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone.
- Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body.
Between visits, participants with a suspected or confirmed variant will keep a diary of disease symptoms and signs.
Samples from all participants may be used for genetic testing
Read the detailed description
Study Description:
This is a natural history study of patients with familial platelet disorder with associated myeloid malignancies (FPDMM), also known as FPD and FPDAML, who undergo diagnostic clinical tests, diagnostic genetic tests, and yearly follow-up visits; and the collected biological samples will be used for biomedical research to understand the disease mechanism, including genomic sequencing. Unaffected family members will participate and serve as controls for studies of the affected family members.
Objectives:
Primary Objective: To identify and follow patients with germline variants in the RUNX1 gene, which leads to FPDMM, an autosomal dominant disorder, with the hope of identifying biomarkers that can predict which patients will progress and develop malignancies, as well as the timing of the progression and the severity of the malignancies.
Secondary Objectives: To identify secondary gene mutations that may impact clinical presentation, disease severity, and progression to malignancies. Secondary gene discovery will distinguish subpopulations of patients and may inform clinical care and improve diagnosis. To profile non-hematopoietic presentations of FPDMM. To identify genetic basis for patients with FPDMM-like clinical presentation but without known RUNX1 variants. To longitudinally assess psychosocial experiences, psychosocial functioning, and health related quality of life of persons living with RUNX1-FPD.
Exploratory Objective: Identify new therapeutic strategies.
Endpoints:
Primary Endpoint: The primary endpoint is progression to malignancy in patients with FPD (FPDMM). Patients who develop malignancies will continue in the study for longitudinal observation.
- Conditions
- Inherited Hematological Diseases, Rare Diseases, FPDMM
- Keywords
- inherited hematological diseases, Rare Diseases, Hematological Malignancies, Cancer, Acute Myeloid Leukemia, Natural History
- Medical subject headings
- Rare Diseases, Platelet Disorder, Familial, with Associated Myeloid Malignancy, Hematologic Neoplasms, Neoplasms, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Family | Direct family members of enrolled patients will be asked to enroll in the study to provide specimens for genetic testing, next-generation sequencing, and other related studies. | |
| RUNX1 | Patients enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natural History
This protocol continues the decades-long tradition of identifying and examining patients with rare genetic diseases and characterizing the natural history.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start28 Mar 2019
- Primary completion31 Dec 2099 (estimated)
- Study completion31 Dec 2099 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Inherited Hematological DiseasesStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paul Liu, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03854318
- Sponsor's protocol ID
- 190059
- Other IDs
- 19-HG-0059
- Status last verified
- 7 Oct 2026
- First submitted
- 22 Feb 2019
- Last updated
- 9 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: pending
Publications
Kajdic A, Deuitch NT, Bresciani E, Chong S, Craft K, Davis J, Bashtawi R, McReynolds LJ, Giri N, Young DJ, Liu PP. Hematologic malignancies in pediatric patients with RUNX1-familial platelet disorder with associated myeloid malignancy. Blood Adv. 2026 May 12;10(9):3075-3085. doi: 10.1182/bloodadvances.2025017808.
PubMed 41616279Yu K, Deuitch N, Merguerian M, Cunningham L, Davis J, Bresciani E, Diemer J, Andrews E, Young A, Donovan F, Sood R, Craft K, Chong S, Chandrasekharappa S, Mullikin J, Liu PP. Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy. Blood Adv. 2024 Jan 23;8(2):497-511. doi: 10.1182/bloodadvances.2023011165.
PubMed 38019014Cunningham L, Merguerian M, Calvo KR, Davis J, Deuitch NT, Dulau-Florea A, Patel N, Yu K, Sacco K, Bhattacharya S, Passi M, Ozkaya N, De Leon S, Chong S, Craft K, Diemer J, Bresciani E, O'Brien K, Andrews EJ, Park N, Hathaway L, Cowen EW, Heller T, Ryan K, Barochia A, Nghiem K, Niemela J, Rosenzweig S, Young DJ, Frischmeyer-Guerrerio PA, Braylan R, Liu PP. Natural history study of patients with familial platelet disorder with associated myeloid malignancy. Blood. 2023 Dec 21;142(25):2146-2158. doi: 10.1182/blood.2023019746.
PubMed 37738626
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Studies of Patients and Families With Familial Platelet Disorders With Associated Myeloid Malignancy (FPDMM) Caused by RUNX1 Germline Variants or FPDMM-Like Conditions
- ClinicalTrials.gov ID
- NCT03854318
- Acronym / sponsor ID
- 190059
- Conditions
- Inherited Hematological Diseases, Rare Diseases, FPDMM
- Keywords
- inherited hematological diseases, Rare Diseases, Hematological Malignancies, Cancer, Acute Myeloid Leukemia, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 28 Mar 2019 (actual)
- Primary completion
- 31 Dec 2099 (estimated)
- Study completion
- 31 Dec 2099 (estimated)
- First posted
- 26 Feb 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.
Background:
Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 variants and FPD.
Objective:
To learn more about FPD in people with RUNX1 variants to lead to better diagnosis, monitoring, and treatment.
Eligibility:
People any age with a suspected or confirmed RUNX1 variant
People who have a family member with the variant
Design:
All participants will be screened with a phone call and a blood, saliva, or cheek cell sample.
Participants with a suspected or confirmed variant will have 1 visit. It will last about 2 days. They will then have visits at least once a year.
Visits will include:
- Medical history and physical exam
- Blood tests or saliva sample
- Possible skin biopsy: A small piece of the participant s skin will be removed.
- Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone.
- Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body.
Between visits, participants with a suspected or confirmed variant will keep a diary of disease symptoms and signs.
Samples from all participants may be used for genetic testing
Detailed description
Study Description:
This is a natural history study of patients with familial platelet disorder with associated myeloid malignancies (FPDMM), also known as FPD and FPDAML, who undergo diagnostic clinical tests, diagnostic genetic tests, and yearly follow-up visits; and the collected biological samples will be used for biomedical research to understand the disease mechanism, including genomic sequencing. Unaffected family members will participate and serve as controls for studies of the affected family members.
Objectives:
Primary Objective: To identify and follow patients with germline variants in the RUNX1 gene, which leads to FPDMM, an autosomal dominant disorder, with the hope of identifying biomarkers that can predict which patients will progress and develop malignancies, as well as the timing of the progression and the severity of the malignancies.
Secondary Objectives: To identify secondary gene mutations that may impact clinical presentation, disease severity, and progression to malignancies. Secondary gene discovery will distinguish subpopulations of patients and may inform clinical care and improve diagnosis. To profile non-hematopoietic presentations of FPDMM. To identify genetic basis for patients with FPDMM-like clinical presentation but without known RUNX1 variants. To longitudinally assess psychosocial experiences, psychosocial functioning, and health related quality of life of persons living with RUNX1-FPD.
Exploratory Objective: Identify new therapeutic strategies.
Endpoints:
Primary Endpoint: The primary endpoint is progression to malignancy in patients with FPD (FPDMM). Patients who develop malignancies will continue in the study for longitudinal observation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Family | – | –Direct family members of enrolled patients will be asked to enroll in the study to provide specimens for genetic testing, next-generation sequencing, and other related studies. |
| RUNX1 | – | –Patients enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation. |
Who may qualify
- Ages
- 1 day to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients (and direct family members of patients) enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation.
Key inclusion criteria (1 listed)
- Patients enrolled in this protocol will have been referred with a known or suspected variant in the RUNX1 gene. Patients with suspected RUNX1 variants are those with clinical features of FPD but who have not been tested for RUNX1, or who were negative on standard testing. The Principal Investigator, along with consulting specialists, will review the medical records of prospective patients and offer enrollment based upon the potential to help the individual, to learn from the patient, or to initiate clinical or basic research suggested by the patient's workup. Persons interested in participation may be given a screening questionnaire to determine eligibility. The questions about hematologic manifestations in the screening questionnaire are important to help us determine if RUNX1 variants are likely to be pathogenic, or if there is a high clinical suspicion of RUNX1 (abnormal platelets, bleeding, bruising, leukemia etc.). Unaffected family members may be asked to enroll in the study to provide specimens (saliva, blood, skin) for genetic testing, next-generation sequencing, and other related studies. Enrolled subjects can be any sex and any age. There are no upper or lower age restrictions on this study.
Key exclusion criteria (1 listed)
- There are no exclusionary criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Natural History
Time frame: Ongoing
This protocol continues the decades-long tradition of identifying and examining patients with rare genetic diseases and characterizing the natural history.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Derived from this study: PubMed 41616279Kajdic A, Deuitch NT, Bresciani E, Chong S, Craft K, Davis J, Bashtawi R, McReynolds LJ, Giri N, Young DJ, Liu PP. Hematologic malignancies in pediatric patients with RUNX1-familial platelet disorder with associated myeloid malignancy. Blood Adv. 2026 May 12;10(9):3075-3085. doi: 10.1182/bloodadvances.2025017808.
- Derived from this study: PubMed 38019014Yu K, Deuitch N, Merguerian M, Cunningham L, Davis J, Bresciani E, Diemer J, Andrews E, Young A, Donovan F, Sood R, Craft K, Chong S, Chandrasekharappa S, Mullikin J, Liu PP. Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy. Blood Adv. 2024 Jan 23;8(2):497-511. doi: 10.1182/bloodadvances.2023011165.
- Derived from this study: PubMed 37738626Cunningham L, Merguerian M, Calvo KR, Davis J, Deuitch NT, Dulau-Florea A, Patel N, Yu K, Sacco K, Bhattacharya S, Passi M, Ozkaya N, De Leon S, Chong S, Craft K, Diemer J, Bresciani E, O'Brien K, Andrews EJ, Park N, Hathaway L, Cowen EW, Heller T, Ryan K, Barochia A, Nghiem K, Niemela J, Rosenzweig S, Young DJ, Frischmeyer-Guerrerio PA, Braylan R, Liu PP. Natural history study of patients with familial platelet disorder with associated myeloid malignancy. Blood. 2023 Dec 21;142(25):2146-2158. doi: 10.1182/blood.2023019746.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. pending
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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.
Paul Liu, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inherited Hematological Diseases and Rare Diseases, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 9 Oct 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natalie T Deuitch ((301) 385-5205, natalie.deuitch@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Natural History (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03854318, which also lists 3 linked publications.
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 9 Oct 2026.