Clonal Architecture of ASXL1-mutated Myelofibrosis (CLONEMF)

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

Study Overview

• Status: Recruiting
• Conditions: Myelofibrosis
• Intervention / Treatment: Biological: Clonal architecture determination

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 Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margaux Wiber, PharmD.; Phone Number: 0033241355553; Email: margaux.wiber@chu-angers.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • Chu Angers
    • Contact: Corentin ORVAIN, Dr
    • Principal Investigator: Corentin ORVAIN, Dr
  • Brest, France
    • Not yet recruiting
    • CHRU BREST
    • Contact: Jean-Christophe IANOTTO, Pr
    • Principal Investigator: Jean-Christophe IANOTTO, Pr
  • Cholet, France
    • Not yet recruiting
    • CH Cholet
    • Contact: Charles BESCOND, Dr
    • Principal Investigator: Charles BESCOND, Dr
  • Créteil, France, 94010
    • Recruiting
    • CHU Henri Mondor
    • Contact: Lydia ROY; Phone Number: +33 01 49 81 20 57; Email: lydia.roy@aphp.fr
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
    • Contact: Jérôme REY; Phone Number: +33 04 91 22 36 95; Email: reyj@ipc.unicancer.fr
  • Nantes, France
    • Not yet recruiting
    • Chu Nantes
    • Contact: Viviane DUBRUILLE, Dr
    • Principal Investigator: Viviane DUBRUILLE, Dr
  • Paris, France
    • Recruiting
    • Hôpital Bicêtre
    • Contact: Laurence Laurence, Dr
    • Principal Investigator: Laurence Laurence, Dr
  • Paris, France, 75010
    • Not yet recruiting
    • AP-HP Hôpital Saint Louis
    • Contact: Juliette SORET-DULPHY; Phone Number: +33 04 42 49 47 87; Email: Juliette.soret@aphp.fr
  • Pessac, France, 33604
    • Recruiting
    • CHU de Bordeaux
    • Contact: Clémence MEDIAVILLA; Phone Number: +33 05 57 65 65 11; Email: clemence.mediavilla@chu-bordeaux.fr
  • Pierre-Bénite, France, 69495
    • Recruiting
    • CHU Lyon
    • Contact: Vincent ALCAZER; Phone Number: +33 04 78 86 43 12; Email: vincent.alcazer@chu-lyon.fr
  • Quimper, France
    • Not yet recruiting
    • CH de Cornouaille
    • Contact: Lenaïg LE CLECH, Dr
    • Principal Investigator: Lenaïg LE CLECH, Dr
  • Tours, France
    • Recruiting
    • CHRU Tours - Hôpital Bretonneau
    • Principal Investigator: Antoine MACHET, Dr
    • Contact: Antoine MACHET, Dr
  • Vannes, France
    • Not yet recruiting
    • CH de Vannes
    • Contact: Mélanie MERCIER; Phone Number: +33 02 97 01 48 45; Email: melanie.mercier@ch-bretagne-atlantique.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify subgroups of ASXL1-mutated myelofibrosis based on clonal architecture data	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.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of previously constituted prognostic genomic groups (according to Luque Paz et al. 2021) within identified clusters of clonal architecture	The repartition of patients onto genomic groups will be reported for each clusters of clonal architecture (number and percentage).	24 months
Studying the functional characteristics of each subtype of clonal architecture by transcriptomics	Gene Set Enrichment Analysis (GSEA) will be performed for each cluster of clonal architecture	24 months
Comparison of male proportion within the subtypes of clonal architecture	Repartition of gender will be compared	24 months
Comparison of age at the time of diagnosis within the subtypes of clonal architecture	Age at the time (years) of diagnosis will be compared	24 months
Comparison of blood counts within the subtypes of clonal architecture	Blood counts (g/dL or G/L) at the time of diagnosis will be compared	24 months
Comparison of LDH levels within the subtypes of clonal architecture	LDH levels (UI/L) at the time of diagnosis will be compared	24 months
Comparison of splenomegaly proportion within the subtypes of clonal architecture	Proportion of patients with splenomegaly will be compared	24 months
Comparison of constitutional symptoms proportion within the subtypes of clonal architecture	Proportion of patients with constitutional symptoms will be compared	24 months
Evaluation of overall survival of the patients at 4 years according to their clonal architecture profile	Overall survival will be evaluated by Cox models	72 months
Evaluation of the leukemia-free survival of the patients at 4 years according to their clonal architecture profile	Leukemia-free survival will be evaluated by Cox models	72 months

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Study Director: POUILLART, University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): April 23, 2027
• Study Completion (Estimated): April 23, 2031

Study Registration Dates

• First Submitted: December 28, 2022
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Hemic and Lymphatic Diseases; Primary Myelofibrosis
• Other Study ID Numbers: 2022-A02497-36

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No