Clonal Architecture of ASXL1-mutated Myelofibrosis

Myelofibrosis Clinical Trial

— CLONEMF  

Official title:

Clonal Architecture of ASXL1-mutated Myelofibrosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05710211
• Other study ID #: 2022-A02497-36
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2023
• Est. completion date: March 2029

Study information

• Verified date: December 2022
• Source: University Hospital, Angers
• Contact: Margaux Wiber, PharmD.
• Phone: 0033241355553
• Email: margaux.wiber[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 2029
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

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

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHRU Brest	Brest
France	CH Cholet	Cholet
France	CHU Nantes	Nantes
France	Hôpital Bicêtre	Paris
France	CH de Cornouaille	Quimper
France	CHRU Tours - Hôpital Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Comparison of male proportion within the subtypes of clonal architecture	Repartition of gender will be compared	24 months
Secondary	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
Secondary	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
Secondary	Comparison of LDH levels within the subtypes of clonal architecture	LDH levels (UI/L) at the time of diagnosis will be compared	24 months
Secondary	Comparison of splenomegaly proportion within the subtypes of clonal architecture	Proportion of patients with splenomegaly will be compared	24 months
Secondary	Comparison of constitutional symptoms proportion within the subtypes of clonal architecture	Proportion of patients with constitutional symptoms will be compared	24 months
Secondary	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
Secondary	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