Longitudinal Studies of Patient With FPDMM

• ClinicalTrials.gov Identifier: NCT03854318
• Recruitment Status: Recruiting
• First Posted: February 26, 2019
• Last Update Posted: March 19, 2020
• Sponsor: National Human Genome Research Institute (NHGRI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Study Description

Brief Summary:

Inherited mutations in RUNX1 are responsible for familial platelet disorder with associated myeloid malignancies (FPDMM, or simply FPD), an autosomal dominant disease characterized by defective megakaryocytic development, low platelet counts, prolonged bleeding times, and a life-long risk of developing hematological malignancies. Disease penetrance and clinical presentations vary among families with different germline RUNX1 mutations, and even among affected individuals within a single family. Currently there are no biomarkers or assays to predict which patients will progress to malignancy, and some patients present with AML as their initial manifestation of the germline syndrome. We propose to characterize the etiology and natural history of patients with RUNX1 mutations, both known and yet-to-be discovered. In so doing, we will expand our knowledge about this disorder and provide access to patients of interest for research, teaching, and clinical experience. The knowledge gained through this study will lead to better understanding of the disease progression, both clinically and at a molecular level, which may result in the development of better diagnosis, monitoring, and innovative therapies.

Condition or disease
Inherited Hematological Diseases; Rare Diseases; FPDMM

Detailed Description:

Inherited mutations in RUNX1 are responsible for familial platelet disorder with associated myeloid malignancies (FPDMM, or simply FPD), an autosomal dominant disease characterized by defective megakaryocytic development, low platelet counts, prolonged bleeding times, and a life-long risk of developing hematological malignancies. Disease penetrance and clinical presentations vary among families with different germline RUNX1 mutations, and even among affected individuals within a single family. Currently there are no biomarkers or assays to predict which patients will progress to malignancy, and some patients present with AML as their initial manifestation of the germline syndrome. We propose to characterize the etiology and natural history of patients with RUNX1 mutations, both known and yet-to-be discovered. In so doing, we will expand our knowledge about this disorder and provide access to patients of interest for research, teaching, and clinical experience. The knowledge gained through this study will lead to better understanding of the disease progression, both clinically and at a molecular level, which may result in the development of better diagnosis, monitoring, and innovative therapies.

Study Design

• Study Type: Observational
• Estimated Enrollment: 1000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Longitudinal Studies of Patient With FPDMM
• Actual Study Start Date: March 28, 2019
• Estimated Primary Completion Date: December 31, 2028
• Estimated Study Completion Date: December 31, 2028

Groups and Cohorts

Group/Cohort
Family; Direct family members of enrolled patients will be asked to enroll in the study to providespecimens 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 RUNX1mutation.

Outcome Measures

Primary Outcome Measures :

1. Natural History [ Time Frame: Ongoing ]
   This protocol continues the decades-long tradition of identifying and examining patients with rare genetic diseases and characterizingthe natural history.

Eligibility Criteria

• Ages Eligible for Study: 8 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Patients (and direct family members of patients) enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation.

Criteria

• INCLUSION CRITIERIA:
• Patients enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation.
• Direct family members of enrolled patients will be asked to enroll in the study to provide specimens (blood, saliva, or buccal swabs) for genetic testing, next-generation sequencing, and other related studies.
• Enrolled subjects (patients and unaffected family members) must be one month of age or older.

EXCLUSION CRITIERIA:

-Prisoners

Contacts and Locations

Contacts

Contact: Paul P Liu, M.D.; (301) 402-2529; pliu@nhgri.nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Human Genome Research Institute (NHGRI)

Investigators

• Principal Investigator: Paul P Liu, M.D.; National Human Genome Research Institute (NHGRI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Human Genome Research Institute (NHGRI)
• ClinicalTrials.gov Identifier: NCT03854318
• Other Study ID Numbers: 190059; 19-HG-0059
• First Posted: February 26, 2019
• Last Update Posted: March 19, 2020
• Last Verified: March 17, 2020

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) ):

inherited hematological diseases; Rare Diseases; Hematological Malignancies; Cancer; Acute Myeloid Leukemia

Additional relevant MeSH terms:

Hematologic Diseases; Rare Diseases; Disease Attributes; Pathologic Processes