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NCT Number: NCT05710211

Clonal Architecture of ASXL1-mutated Myelofibrosis

Prospective study to decipher the clonal architecture of ASXL1-mutated primary and secondary myelofibrosis and its impact on prognosis

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Key information

Conditions

Myelofibrosis Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Myeloproliferative Disorders Primary Myelofibrosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU Angers, Angers, France

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About this study

The clonal architecture of myelofibrosis patients is still little described. Inconsistent results in terms of the prognostic value of some mutations are observed in the literature, in particular concerning ASXL1 mutations. We assume that a better understanding of the clonal architecture of ASXL1-mutated myelofibrosis could help refining the prognostic impact of ASXL1 mutations.

This study aims to evaluate a multicenter cohort of 50 patients. Blood of patients will be collected within 18 months of diagnosis. After 4 years of follow-up of the patient as part of his usual care, data on survival and leukemic transformation will be collected.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults (age ≥18 years),
  • Affiliated to the national social security system,
  • ASXL1 mutated primary or secondary myelofibrosis,
  • Signed the consent to participate in the study,
  • Included, or consenting to be included, in the national clinical-biological database of France Intergroupe Syndrome Myéloprolifératifs (FIM).

Exclusion criteria

  • Patient with another active hematological disease or cancer at the time of diagnosis,
  • Person subject to legal protection scheme or incapable of giving consent.

Treatment and study plan

Clonal architecture determination

Biological

Biological:

  • Determination of clonal architecture by sorting of circulating CD34 positive cells followed by cell culture and colony genotyping and/or single-cell DNA-sequencing
  • Secondary outcome: transcriptomic study by RNA-sequencing

Primary outcomes

  1. Identify subgroups of ASXL1-mutated myelofibrosis based on clonal architecture data

    Time frame: 24 months

    The clonal architecture is defined by the number of mutations (numerical), the order of acquisition of the mutations (categorial, pre/post/separated), the mutational branching (categorial, yes/no), the presence of distinct clones (categorial, yes/no) and the transition towards homozygosity of each clone (categorial, yes/no). All parameters of clonal architecture will be analyzed together using a multivariate classification (Factor Analysis for Mixed Data) followed by a clustering which allow us to identify homogeneous cluster of patients.

Secondary outcomes

  1. Description of previously constituted prognostic genomic groups (according to Luque Paz et al. 2021) within identified clusters of clonal architecture

    Time frame: 24 months

    The repartition of patients onto genomic groups will be reported for each clusters of clonal architecture (number and percentage).

  2. Studying the functional characteristics of each subtype of clonal architecture by transcriptomics

    Time frame: 24 months

    Gene Set Enrichment Analysis (GSEA) will be performed for each cluster of clonal architecture

  3. Comparison of male proportion within the subtypes of clonal architecture

    Time frame: 24 months

    Repartition of gender will be compared

  4. Comparison of age at the time of diagnosis within the subtypes of clonal architecture

    Time frame: 24 months

    Age at the time (years) of diagnosis will be compared

  5. Comparison of blood counts within the subtypes of clonal architecture

    Time frame: 24 months

    Blood counts (g/dL or G/L) at the time of diagnosis will be compared

  6. Comparison of LDH levels within the subtypes of clonal architecture

    Time frame: 24 months

    LDH levels (UI/L) at the time of diagnosis will be compared

  7. Comparison of splenomegaly proportion within the subtypes of clonal architecture

    Time frame: 24 months

    Proportion of patients with splenomegaly will be compared

  8. Comparison of constitutional symptoms proportion within the subtypes of clonal architecture

    Time frame: 24 months

    Proportion of patients with constitutional symptoms will be compared

  9. Evaluation of overall survival of the patients at 4 years according to their clonal architecture profile

    Time frame: 72 months

    Overall survival will be evaluated by Cox models

  10. Evaluation of the leukemia-free survival of the patients at 4 years according to their clonal architecture profile

    Time frame: 72 months

    Leukemia-free survival will be evaluated by Cox models

Study contacts

Contact information is provided by the study sponsor or research team.

Margaux Wiber, PharmD.

CONTACT

[email protected]

0033241355553

Sponsors and collaborators

Lead sponsor

University Hospital, Angers

Other Gov

Registry information

Acronym: CLONEMF

Important dates

Study start
2023
Primary completion
2027
Study completion
2031
First posted
Feb 2, 2023
Registry last updated
Mar 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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