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Clonal Architecture of ASXL1-mutated Myelofibrosis (CLONEMF)

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ClinicalTrials.gov Identifier: NCT05710211
Recruitment Status : Not yet recruiting
First Posted : February 2, 2023
Last Update Posted : February 2, 2023
Sponsor:
Information provided by (Responsible Party):
University Hospital, Angers

Study Description
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Brief Summary:
Prospective study to decipher the clonal architecture of ASXL1-mutated primary and secondary myelofibrosis and its impact on prognosis

Condition or disease Intervention/treatment Phase
Myelofibrosis Biological: Clonal architecture determination Not Applicable

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Clonal Architecture of ASXL1-mutated Myelofibrosis
Estimated Study Start Date : March 2023
Estimated Primary Completion Date : March 2025
Estimated Study Completion Date : March 2029

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Arms and Interventions
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Arm Intervention/treatment
Experimental: CLONEMF cohort Biological: Clonal architecture determination

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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05710211


Contacts
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Contact: Margaux Wiber, PharmD. 0033241355553 margaux.wiber@chu-angers.fr

Locations
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France
CHU Angers
Angers, France
Contact: Corentin ORVAIN, Dr         
Principal Investigator: Corentin ORVAIN, Dr         
CHRU Brest
Brest, France
Contact: Jean-Christophe IANOTTO, Pr         
Principal Investigator: Jean-Christophe IANOTTO, Pr         
CH Cholet
Cholet, France
Contact: Charles BESCOND, Dr         
Principal Investigator: Charles BESCOND, Dr         
CHU Nantes
Nantes, France
Contact: Viviane DUBRUILLE, Dr         
Principal Investigator: Viviane DUBRUILLE, Dr         
Hôpital Bicêtre
Paris, France
Contact: Laurence Laurence, Dr         
Principal Investigator: Laurence Laurence, Dr         
CH de Cornouaille
Quimper, France
Contact: Lenaïg LE CLECH, Dr         
Principal Investigator: Lenaïg LE CLECH, Dr         
CHRU Tours - Hôpital Bretonneau
Tours, France
Contact: Antoine MACHET, Dr         
Principal Investigator: Antoine MACHET, Dr         
Sponsors and Collaborators
University Hospital, Angers
Investigators
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Study Director: POUILLART University Hospital, Angers
More Information
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Responsible Party: University Hospital, Angers
ClinicalTrials.gov Identifier: NCT05710211    
Other Study ID Numbers: 2022-A02497-36
First Posted: February 2, 2023    Key Record Dates
Last Update Posted: February 2, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases