Clonal Architecture of ASXL1-mutated Myelofibrosis
- Conditions
- Myelofibrosis
- Interventions
- Biological: Clonal architecture determination
- Registration Number
- NCT05710211
- Lead Sponsor
- University Hospital, Angers
- Brief Summary
Prospective study to decipher the clonal architecture of ASXL1-mutated primary and secondary myelofibrosis and its impact on prognosis
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
- 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).
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CLONEMF cohort Clonal architecture determination -
- Primary Outcome Measures
Name Time Method Identify subgroups of ASXL1-mutated myelofibrosis based on clonal architecture data 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
Name Time Method Description of previously constituted prognostic genomic groups (according to Luque Paz et al. 2021) within identified clusters of clonal architecture 24 months The repartition of patients onto genomic groups will be reported for each clusters of clonal architecture (number and percentage).
Studying the functional characteristics of each subtype of clonal architecture by transcriptomics 24 months Gene Set Enrichment Analysis (GSEA) will be performed for each cluster of clonal architecture
Comparison of male proportion within the subtypes of clonal architecture 24 months Repartition of gender will be compared
Comparison of splenomegaly proportion within the subtypes of clonal architecture 24 months Proportion of patients with splenomegaly will be compared
Evaluation of overall survival of the patients at 4 years according to their clonal architecture profile 72 months Overall survival will be evaluated by Cox models
Comparison of age at the time of diagnosis within the subtypes of clonal architecture 24 months Age at the time (years) of diagnosis will be compared
Comparison of blood counts within the subtypes of clonal architecture 24 months Blood counts (g/dL or G/L) at the time of diagnosis will be compared
Comparison of LDH levels within the subtypes of clonal architecture 24 months LDH levels (UI/L) at the time of diagnosis will be compared
Comparison of constitutional symptoms proportion within the subtypes of clonal architecture 24 months Proportion of patients with constitutional symptoms will be compared
Evaluation of the leukemia-free survival of the patients at 4 years according to their clonal architecture profile 72 months Leukemia-free survival will be evaluated by Cox models
Trial Locations
- Locations (13)
CHU Henri MONDOR
🇫🇷Creteil, France
CH Cholet
🇫🇷Cholet, France
CH de Cornouaille
🇫🇷Quimper, France
CHRU Tours - Hôpital Bretonneau
🇫🇷Tours, France
CHU Nantes
🇫🇷Nantes, France
CHU de Bordeaux
🇫🇷Pessac, France
CHU Lyon
🇫🇷Pierre Bénite, France
CHRU Brest
🇫🇷Brest, France
CH de Vannes
🇫🇷Vannes, France
Institut Paoli Calmettes
🇫🇷Marseille, France
AP-HP Hôpital Saint Louis
🇫🇷Paris, France
Hôpital Bicêtre
🇫🇷Paris, France
CHU Angers
🇫🇷Angers, France