Recruiting

Bone Marrow FailureNatural History of Acquired and Inherited Bone Marrow Failure Syndromes

Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Code:

NCT05012111

Conditions

Severe Aplastic Anemia

Telomere Biology Disorders

Inherited Bone Marrow Failure Syndromes

Eligibility Criteria

Sex: All

Age: 2 - 70+

Healthy Volunteers: Not accepted

Study Details

Brief summary:

Background:

Bone marrow failure diseases are rare. Much is known about the diseases at the time of diagnosis, but long-term data about the effects of the diseases and treatments are lacking. Researchers want to better understand long-term outcomes in people with these diseases.

Objective:

To follow people diagnosed with acquired or inherited bone marrow failure disease and study the long-term effects of the disease and its treatments on organ function.

Eligibility:

People aged 2 years and older who have been diagnosed with acquired or inherited bone marrow failure or Telomere Biology Disorder. First degree family members may also be able to take part in the study.

Design:

Participants will be screened with a medical history, physical exam, and blood tests. They may have a bone marrow biopsy and aspiration. For this, a large needle will be inserted in the hip through a small cut. Marrow will be drawn from the bone. A small piece of bone may be removed.

Participants may also be screened with some of the following:

Cheek swab or hair follicle sample

Skin biopsy

Urine or saliva sample

Evaluation by disease specialists (e.g., lung, liver, heart)

Imaging scan of the chest

Liver ultrasounds

Six-Minute Walk Test

Lung function test

Participants will be put into groups based on their disease. They will have visits every 1 to 3 years. At visits, they may repeat some screening tests. They may fill out yearly surveys about their medicines, transfusions, pregnancy, bleeding, and so on. They may have other specialized procedures, such as imaging scans and ultrasounds.

Participation will last for up to 20 years.

Conditions

Severe Aplastic Anemia

Telomere Biology Disorders

Inherited Bone Marrow Failure Syndromes

Study ID

NCT05012111

Start date

Oct 25, 2021

Status verified date

Jul 17, 2026

Completion date

Feb 4, 2041

Anticipated

Primary completion date

Feb 4, 2041

Anticipated

Eligibility Criteria

Sex: All

Age: 2 - 70+

Healthy Volunteers: Not accepted

INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria. Subjects and their family members who undergo screening but ultimately do not meet criteria for cohorts 1-5 will be removed from the study. Subjects may forgo screening and sign directly onto cohorts 1-5 if they meet criteria based on either prior NIH testing or external examinations. Family members will only be asked to be screened for participation onto this study after confirmation of eligibility by an affected participant.

Cohorts 1-4

Age >=2 years
Diagnosis of acquired or inherited bone marrow failure or ineffective hematopoiesis or TBD (see below for cohort 3 specific criteria)
Ability and willingness to come to the NIH CC for consultation and testing
Ability of subject or Legally Authorized Representative (LAR) to understand the investigational nature of the protocol and their willingness to sign a written informed consent document.
For cohort 3 - TBD:

Presence of a pathogenic, likely pathogenic, or known family mutation in a telomere maintenance gene

OR

If mutation negative or VUS, telomere length <10th percentile in lymphocytes with at least two clinical features: 1) cytopenia (Hb <10g/dL or ANC <1.5x10\^9 or platelets <100), 2) documented liver fibrosis by histology OR abnormal liver US / fibro scan consistent with fatty liver or fibrosis), 3) documented pulmonary fibrosis by histology / radiology OR PFTs showing FEV1 <80% or DLCO <60%, 4) family history of: marrow failure, myeloid malignancy, liver fibrosis or lung fibrosis.

Cohort 5

Age >= 2 years
First degree family member with a known or suspected inherited bone marrow failure syndrome from a patient enrolled on this or another NIH protocol as determined by a PI or AI
Ability and willingness to safely provide blood, buccal swab, or fibroblasts for testing as stated by subject
Ability of subject or Legally Authorized Representative (LAR) to understand the investigational nature of the protocol and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

-None

Study Design

Enrollment

1000 participants

Anticipated

Interventions and Outcome Measures

Arms

Cohort 1

Severe Aplastic Anemia(SAA): Age 2 and older; Previous diagnosis of bone marrow failure

Cohort 2

Other Marrow Failure: Age 2 and older; Previous diagnosis of bone marrow failure;

Cohort 3

Telomere Biology Disorders(TBD): Age 2 and older; Previous diagnosis of bone marrow failure

Cohort 4

Inherited Bone Marrow Failure(IBMF)Syndromes: Age 2 and older; Previous diagnosis of bone marrow failure

Cohort 5

Family Screening: Age 2 and older; First degree family member with a known or suspected inherited bone marrow failure syndrome

Primary outcome measure

Cohort 4: Rate of progression to transfusion dependent marrow failure, marrow failure requiring therapeutic intervention (such as medical therapy or HSCT) or the progression to hematological malignancy [ Time Frame: 20 years ]
Cohort 3: Development of cytopenias, lung disease or liver disease, or (if present at baseline) characterization, and rate of progression of cytopenias, lung disease or liver disease in TBD patients and looking at their overall contribution to m... [ Time Frame: 20 years ]
Cohort 1: Rate of relapse and clonal evolution in previously treated patients [ Time Frame: 20 years ]
Cohort 2: Rate of progression requiring therapeutic intervention [ Time Frame: 20 years ]

Central Contacts and Locations

Central contacts

Tania R Machado

(301) 661-1505 tania.machado@nih.gov

Emma M Groarke, M.D.

(301) 496-5093 emma.groarke@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222 prpl@cc.nih.gov

More Information

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Last update posted

Aug 27, 2026

Last verified

Jul 17, 2026

Keywords

Aplastic Anemia
Telomere
Natural History

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Heart, Lung, and Blood Institute (NHLBI) on 2026-08-27.