Understanding the natural progression of blood cell disorders

Investigation of the Natural Progression of Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenia of Undetermined Significance.

Observational National Institutes of Health Clinical Center (CC) · NCT04102423

This study is trying to understand how certain blood cell disorders develop over time in adults by looking at their genes and seeing if they are linked to blood cancers and other health issues.

Quick facts

Study typeObservational
Enrollment306 (estimated)
Ages18 Years to 99 Years
SexAll
SponsorNational Institutes of Health Clinical Center (CC) NIH
Locations1 site (Bethesda, Maryland)
Trial IDNCT04102423 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the natural history of Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Clonal Cytopenia of Undetermined Significance (CCUS) in adults. Researchers will screen participants for somatic pathogenic variants associated with blood cancers through blood samples and gene testing. The study seeks to verify the links between these genetic mutations, atherosclerosis, and the development of blood cancers, while also exploring new clinical associations. The findings could enhance understanding of these conditions and their progression.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with CHIP or CCUS and specific somatic pathogenic variants.

Not a fit: Patients with known hematological malignancies or severe cytopenias will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better risk assessment and management strategies for patients with CHIP and CCUS.

How similar studies have performed: While the study focuses on the natural history of these conditions, similar approaches have shown promise in understanding pre-neoplastic phases in other hematological disorders.

Eligibility criteria

Show full inclusion / exclusion criteria
* Participants with Clonal Hematopoiesis of Indeterminate Significance (CHIP):

INCLUSION CRITERIA:

* Greater than or equal to 18 years of age
* Willingness and capacity to provide written informed consent
* Presence of a somatic pathogenic variant associated with hematological malignancy
* Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant

EXCLUSION CRITERIA:

* Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
* Presence of a cytopenia:

  --Hemoglobin, \<10 g/dL; platelet count, \<100 X 10\^9 /L; or absolute neutrophil count, \<1.5 X 10\^9 /L
* Pregnant at the time of recruitment

Participants with Clonal Cytopenia of Uncertain Significance (CCUS):

INCLUSION CRITERIA:

* Greater than 18 years of age
* Willingness and capacity to provide written informed consent
* Presence of a somatic pathogenic variant associated with hematological malignancy without morphological evidence of

myelodysplasia and without a MDS defining cytogenetic abnormality

* Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant
* Bone marrow aspirate and biopsy excluding hematological malignancy and MDS
* Presence of a cytopenia for \>30 days

  * Hemoglobin, \<10 g/dL; platelet count, \<100 X10\^9 /L; or absolute neutrophil count, \<1.5 X10\^9 /L
  * At least 2 CBCs documented in a non-hospitalized patient at least 3 days apart

EXCLUSION CRITERIA:

* Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
* Morphological evidence of dysplasia on bone marrow aspirate / biopsy 10% dysplastic cells in any hematopoietic lineage
* Ringed sideroblasts \>15%
* Presence of MDS defining cytogenetic abnormality

  * Del(7q)
  * del(5q)
  * 17q or t(17p)
  * Del(13q)
  * del(11q)
  * del(12p) or t(12p)
  * del(9q)
  * idic(X)(q13)
  * t(11;16)
  * t(3;21)
  * t(1;3)
  * t(2;11)
  * inv(3)/t(3;3)
* t(6;9)

  --Note: As a sole cytogenetic abnormality in the absence of morphological criteria, gain of chromosome 8, del(20q) and loss of chromosome Y are not considered definitive evidence of MDS.
* Alternate hematological diagnosis causing cytopenia
* Pregnant at time of recruitment

Where this trial is running

Bethesda, Maryland

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Clonal Hematopoiesis of Indeterminate PotentialClonal Cytopenia of Undetermined SignificanceCytopeniaMyelodysplastic SyndromeSomatic MutationsNatural History
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.