Bone Marrow Failure DisordersNCT07102849
Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study
An observational study of Bone Marrow Failure Disorders and VEXAS Syndrome, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
STUDY DESCRIPTION: Bone marrow failure can result from immune mediated attack on stem cells or from inherited genetic defects such as telomere biology disorders or Fanconi anemia. Aplastic anemia (AA), a prototype of bone marrow failure syndromes (BMFS), can be acquired or inherited. Read more about this study
- Who is it for?
- Ages 2 to 120 years
- Conditions the study is for
- Bone Marrow Failure Disorders, VEXAS Syndrome, Hemoglobinurea, Paroxysmal
- Type of treatment
- Pill or oral medicine
- How many people
- 1,400 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2025to 11 Jul 2030
- 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 2 to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: This study will utilize biospecimens and data with identifiers from up to 1,400 research participants with BMFS, aged 2 years and older, alongside age matched healthy volunteers aged 8 years and older.
- This study will utilize biospecimens and data with identifiers from up to 1,400 research participants with BMFS, aged 2 years and older, alongside age matched healthy volunteers aged 8 years and older.
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
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: In-Depth Molecular Characterization in Marrow Failure Syndromes to Understand Clonal Dynamics and Expansion
STUDY DESCRIPTION:
Bone marrow failure can result from immune mediated attack on stem cells or from inherited genetic defects such as telomere biology disorders or Fanconi anemia. Aplastic anemia (AA), a prototype of bone marrow failure syndromes (BMFS), can be acquired or inherited. Acquired BMFS have common immune mediated pathophysiology, and include AA, lower risk myelodysplastic syndrome (MDS, particularly hypoMDS), VEXAS, large granular lymphocytosis (LGL), paroxysmal nocturnal hemoglobinuria (PNH), pure red cell aplasia (PRCA), or cytopenia of undetermined origin. Clonality is frequent in patients with BMFS. Patients with acquired AA are known to have somatic mutations in phosphatidylinositol glycan class A (PIGA), BCL6 corepressor (BCOR) and HLA genes, which are all related to the immune mediated pathophysiology and good predictors of treatment and overall outcomes. Others such as ASXL1, RUNX1, and splicing factor mutations and/or chromosome 7 aneuploidy are associated with secondary myeloid neoplasms in these patients. Somatic mutations in STAT, DNMT3A and TET2 are prevalent in many other BMFS, such as LGL and VEXAS. Except for acquired AA, the clonal dynamics and trajectories, and cooccurrence of these aberrations in other BMFS are poorly understood. How these clonal events interact with epigenetic and proteomic changes are also unknown. In addition, the role of novel genetic defects in marrow failure is poorly characterized, such as mutations associated with inborn errors of immunity or complement pathways. Our aim is to elucidate this further using multi-omics, bulk/single cell DNA and RNA techniques as well as understand the epigenetics using ATAC-seq, and proteomics. The translation work will be correlated with clinical outcomes and laboratory parameters of patients with the particular BMFS cohort being investigated.
Read more
OBJECTIVES:
Primary Objective: To characterize the molecular aberrations in BMFS and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of hematopoietic stem and progenitor cells (HSPC), immune cells and other cellular composition in peripheral blood and bone marrow samples.
Secondary Objectives:
- To correlate the molecular findings with disease presentation and clinical outcomes (response to treatment, clonal evolution to secondary myeloid neoplasm, survival)
- To correlate molecular findings with clinical laboratory data, cytokine, chemokine, soluble receptor levels and growth factors
- To correlate findings with peripheral or marrow flow cytometry phenotyping
- To correlate findings on this study with already performed germline or somatic mutational data
- To compare the genomic, epigenomic and proteomic findings with healthy age matched controls
Read the detailed description
STUDY DESCRIPTION:
Bone marrow failure can result from immune mediated attack on stem cells or from inherited genetic defects such as telomere biology disorders or Fanconi anemia. Aplastic anemia (AA), a prototype of bone marrow failure syndromes (BMFS), can be acquired or inherited. Acquired BMFS have common immune mediated pathophysiology, and include AA, lower risk myelodysplastic syndrome (MDS, particularly hypoMDS), VEXAS, large granular lymphocytosis (LGL), paroxysmal nocturnal hemoglobinuria (PNH), pure red cell aplasia (PRCA), or cytopenia of undetermined origin. Clonality is frequent in patients with BMFS. Patients with acquired AA are known to have somatic mutations in phosphatidylinositol glycan class A (PIGA), BCL6 corepressor (BCOR) and HLA genes, which are all related to the immune mediated pathophysiology and good predictors of treatment and overall outcomes. Others such as ASXL1, RUNX1, and splicing factor mutations and/or chromosome 7 aneuploidy are associated with secondary myeloid neoplasms in these patients. Somatic mutations in STAT, DNMT3A and TET2 are prevalent in many other BMFS, such as LGL and VEXAS. Except for acquired AA, the clonal dynamics and trajectories, and cooccurrence of these aberrations in other BMFS are poorly understood. How these clonal events interact with epigenetic and proteomic changes are also unknown. In addition, the role of novel genetic defects in marrow failure is poorly characterized, such as mutations associated with inborn errors of immunity or complement pathways. Our aim is to elucidate this further using multi-omics, bulk/single cell DNA and RNA techniques as well as understand the epigenetics using ATAC-seq, and proteomics. The translation work will be correlated with clinical outcomes and laboratory parameters of patients with the particular BMFS cohort being investigated.
OBJECTIVES:
Primary Objective: To characterize the molecular aberrations in BMFS and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of hematopoietic stem and progenitor cells (HSPC), immune cells and other cellular composition in peripheral blood and bone marrow samples.
Secondary Objectives:
- To correlate the molecular findings with disease presentation and clinical outcomes (response to treatment, clonal evolution to secondary myeloid neoplasm, survival)
- To correlate molecular findings with clinical laboratory data, cytokine, chemokine, soluble receptor levels and growth factors
- To correlate findings with peripheral or marrow flow cytometry phenotyping
- To correlate findings on this study with already performed germline or somatic mutational data
- To compare the genomic, epigenomic and proteomic findings with healthy age matched controls
- Conditions
- Bone Marrow Failure Disorders, VEXAS Syndrome, Hemoglobinurea, Paroxysmal, Myelodysplastic Syndromes, Bone Marrow Diseases
- Keywords
- Bone Marrow Failure, Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria
- Medical subject headings
- Bone Marrow Failure Disorders, VEXAS syndrome, Myelodysplastic Syndromes, Bone Marrow Diseases, Anemia, Aplastic, Hemoglobinuria, Paroxysmal
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 |
|---|---|---|
| Healthy Volunteers | Biospecimens and data from age matched healthy volunteers (age 8 and up) will be used from the following protocol:- 07H0113 Procurement and Analysis of Blood, Bone Marrow, and Buccal Mucosa Samples from Healthy Volunteers to Support Clinical and Translational Research Projects in the NHLBI. | |
| Participants with Bone Marrow Failure Disorders | Biospecimens and data from children and adults with BMFS who participated in the following studies will be used:- 04H0012 "Collection of Tissue Specimens from Patients with Solid Tumors or Blood Disorders and Their HLA-Compatible Family Members"Clinical and research data from children and adults with BMFS who participated in the following studies will be used:- 06H0034 "Three Immunosuppressive Treatment Regimens for Severe Aplastic Anemia"- 12H0150 "Eltrombopag with Standard Immunosuppression for Severe Aplastic Anemia"- 20H0033 "Early Initiation of Oral Therapy with Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA)"- 09H0154 "A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag, in Refractory Aplastic Anemia Patients" |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of molecular aberrations in marrow failure
To characterize the molecular aberrations in marrow failure and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of HSPC, immune cells and other cellular composition in peripheral blood and bone marrow samples.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2025
- Study start9 Sep 2025
- Primary completion11 Jul 2030 (estimated)
- Study completion11 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Marrow Failure DisordersStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Other
- Enrolment
- 1,400 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Bhavisha A Patel, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07102849
- Sponsor's protocol ID
- 10002422
- Other IDs
- 002422-H
- Status last verified
- 13 Oct 2026
- First submitted
- 2 Aug 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In-Depth Molecular Characterization in Marrow Failure Syndromes to Understand Clonal Dynamics and Expansion
- ClinicalTrials.gov ID
- NCT07102849
- Acronym / sponsor ID
- 10002422
- Conditions
- Bone Marrow Failure Disorders, VEXAS Syndrome, Hemoglobinurea, Paroxysmal, Myelodysplastic Syndromes, Bone Marrow Diseases
- Keywords
- Bone Marrow Failure, Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 1,400 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 9 Sep 2025 (actual)
- Primary completion
- 11 Jul 2030 (estimated)
- Study completion
- 11 Jul 2030 (estimated)
- First posted
- 5 Aug 2025 (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.
STUDY DESCRIPTION:
Bone marrow failure can result from immune mediated attack on stem cells or from inherited genetic defects such as telomere biology disorders or Fanconi anemia. Aplastic anemia (AA), a prototype of bone marrow failure syndromes (BMFS), can be acquired or inherited. Acquired BMFS have common immune mediated pathophysiology, and include AA, lower risk myelodysplastic syndrome (MDS, particularly hypoMDS), VEXAS, large granular lymphocytosis (LGL), paroxysmal nocturnal hemoglobinuria (PNH), pure red cell aplasia (PRCA), or cytopenia of undetermined origin. Clonality is frequent in patients with BMFS. Patients with acquired AA are known to have somatic mutations in phosphatidylinositol glycan class A (PIGA), BCL6 corepressor (BCOR) and HLA genes, which are all related to the immune mediated pathophysiology and good predictors of treatment and overall outcomes. Others such as ASXL1, RUNX1, and splicing factor mutations and/or chromosome 7 aneuploidy are associated with secondary myeloid neoplasms in these patients. Somatic mutations in STAT, DNMT3A and TET2 are prevalent in many other BMFS, such as LGL and VEXAS. Except for acquired AA, the clonal dynamics and trajectories, and cooccurrence of these aberrations in other BMFS are poorly understood. How these clonal events interact with epigenetic and proteomic changes are also unknown. In addition, the role of novel genetic defects in marrow failure is poorly characterized, such as mutations associated with inborn errors of immunity or complement pathways. Our aim is to elucidate this further using multi-omics, bulk/single cell DNA and RNA techniques as well as understand the epigenetics using ATAC-seq, and proteomics. The translation work will be correlated with clinical outcomes and laboratory parameters of patients with the particular BMFS cohort being investigated.
OBJECTIVES:
Primary Objective: To characterize the molecular aberrations in BMFS and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of hematopoietic stem and progenitor cells (HSPC), immune cells and other cellular composition in peripheral blood and bone marrow samples.
Secondary Objectives:
- To correlate the molecular findings with disease presentation and clinical outcomes (response to treatment, clonal evolution to secondary myeloid neoplasm, survival)
- To correlate molecular findings with clinical laboratory data, cytokine, chemokine, soluble receptor levels and growth factors
- To correlate findings with peripheral or marrow flow cytometry phenotyping
- To correlate findings on this study with already performed germline or somatic mutational data
- To compare the genomic, epigenomic and proteomic findings with healthy age matched controls
Detailed description
STUDY DESCRIPTION:
Bone marrow failure can result from immune mediated attack on stem cells or from inherited genetic defects such as telomere biology disorders or Fanconi anemia. Aplastic anemia (AA), a prototype of bone marrow failure syndromes (BMFS), can be acquired or inherited. Acquired BMFS have common immune mediated pathophysiology, and include AA, lower risk myelodysplastic syndrome (MDS, particularly hypoMDS), VEXAS, large granular lymphocytosis (LGL), paroxysmal nocturnal hemoglobinuria (PNH), pure red cell aplasia (PRCA), or cytopenia of undetermined origin. Clonality is frequent in patients with BMFS. Patients with acquired AA are known to have somatic mutations in phosphatidylinositol glycan class A (PIGA), BCL6 corepressor (BCOR) and HLA genes, which are all related to the immune mediated pathophysiology and good predictors of treatment and overall outcomes. Others such as ASXL1, RUNX1, and splicing factor mutations and/or chromosome 7 aneuploidy are associated with secondary myeloid neoplasms in these patients. Somatic mutations in STAT, DNMT3A and TET2 are prevalent in many other BMFS, such as LGL and VEXAS. Except for acquired AA, the clonal dynamics and trajectories, and cooccurrence of these aberrations in other BMFS are poorly understood. How these clonal events interact with epigenetic and proteomic changes are also unknown. In addition, the role of novel genetic defects in marrow failure is poorly characterized, such as mutations associated with inborn errors of immunity or complement pathways. Our aim is to elucidate this further using multi-omics, bulk/single cell DNA and RNA techniques as well as understand the epigenetics using ATAC-seq, and proteomics. The translation work will be correlated with clinical outcomes and laboratory parameters of patients with the particular BMFS cohort being investigated.
OBJECTIVES:
Primary Objective: To characterize the molecular aberrations in BMFS and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of hematopoietic stem and progenitor cells (HSPC), immune cells and other cellular composition in peripheral blood and bone marrow samples.
Secondary Objectives:
- To correlate the molecular findings with disease presentation and clinical outcomes (response to treatment, clonal evolution to secondary myeloid neoplasm, survival)
- To correlate molecular findings with clinical laboratory data, cytokine, chemokine, soluble receptor levels and growth factors
- To correlate findings with peripheral or marrow flow cytometry phenotyping
- To correlate findings on this study with already performed germline or somatic mutational data
- To compare the genomic, epigenomic and proteomic findings with healthy age matched controls
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteers | – | –Biospecimens and data from age matched healthy volunteers (age 8 and up) will be used from the following protocol:- 07H0113 Procurement and Analysis of Blood, Bone Marrow, and Buccal Mucosa Samples from Healthy Volunteers to Support Clinical and Translational Research Projects in the NHLBI. |
| Participants with Bone Marrow Failure Disorders | – | –Biospecimens and data from children and adults with BMFS who participated in the following studies will be used:- 04H0012 "Collection of Tissue Specimens from Patients with Solid Tumors or Blood Disorders and Their HLA-Compatible Family Members"Clinical and research data from children and adults with BMFS who participated in the following studies will be used:- 06H0034 "Three Immunosuppressive Treatment Regimens for Severe Aplastic Anemia"- 12H0150 "Eltrombopag with Standard Immunosuppression for Severe Aplastic Anemia"- 20H0033 "Early Initiation of Oral Therapy with Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA)"- 09H0154 "A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag, in Refractory Aplastic Anemia Patients" |
Who may qualify
- Ages
- 2 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study will utilize biospecimens and data with identifiers from up to 1,400 research participants with BMFS, aged 2 years and older, alongside age matched healthy volunteers aged 8 years and older.
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
Detection of molecular aberrations in marrow failure
Time frame: baseline
To characterize the molecular aberrations in marrow failure and to understand how clonality, epigenetics, and proteomics contribute to hematopoiesis over the course of disease using high resolution multi-omics characterization of HSPC, immune cells and other cellular composition in peripheral blood and bone marrow samples.
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 15 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Bhavisha A Patel, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 Bone Marrow Failure Disorders and VEXAS Syndrome, run by National Heart, Lung, and Blood Institute (NHLBI) 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?
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: enrolling by invitation, as of the sponsor's last update on 15 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection of molecular aberrations in marrow failure (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Oct 2026.