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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

Tracking Information
First Submitted Date  ICMJE December 28, 2022
First Posted Date  ICMJE February 2, 2023
Last Update Posted Date February 2, 2023
Estimated Study Start Date  ICMJE March 2023
Estimated Primary Completion Date March 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2023)		 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2023)
  • 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).
  • 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
  • Comparison of male proportion within the subtypes of clonal architecture [ Time Frame: 24 months ]
    Repartition of gender will be compared
  • 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
  • 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
  • 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
  • Comparison of splenomegaly proportion within the subtypes of clonal architecture [ Time Frame: 24 months ]
    Proportion of patients with splenomegaly will be compared
  • Comparison of constitutional symptoms proportion within the subtypes of clonal architecture [ Time Frame: 24 months ]
    Proportion of patients with constitutional symptoms will be compared
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clonal Architecture of ASXL1-mutated Myelofibrosis
Official Title  ICMJE Clonal Architecture of ASXL1-mutated Myelofibrosis
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Myelofibrosis
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: CLONEMF cohort
Intervention: Biological: Clonal architecture determination
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2023)		 50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2029
Estimated Primary Completion Date March 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Margaux Wiber, PharmD. 0033241355553 margaux.wiber@chu-angers.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05710211
Other Study ID Numbers  ICMJE 2022-A02497-36
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party University Hospital, Angers
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Angers
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: POUILLART University Hospital, Angers
PRS Account University Hospital, Angers
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP