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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT06246006
Other study ID # NIMAO/2023-1/SC01
Secondary ID
Status Active, not recruiting
Phase
First received
Last updated
Start date October 1, 2023
Est. completion date April 2025

Study information

Verified date January 2024
Source Centre Hospitalier Universitaire de Nimes
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The MPL gene is implicated in two groups of hematological pathologies: congenital amegakaryocytic thrombocytopenia (CAMT) and Phi negative myeloproliferative neoplasia (MPN). Fifty germline mutations have been identified in CAMT, yet only a dozen activating mutations have been described in MPN. Most are somatic, distributed mainly in the transmembrane (TM) and juxtamembrane (JM) domains. However, a few rare germline mutations located in the extracellular domain (ECD) have also been reported: K39N, R102P and P106L. Next generation sequencing technology has been used to study the complete MPL gene, identifying numerous variants, most of unknown significance. The study investigators have a series comprising 41 variants of unknown significance, whose allelic frequencies suggest a germline origin for 80% of them. Their distribution within the MPL gene is similar to that of inactivating mutations, except that they were discovered in the context of suspected myeloproliferative disease. Characterizing the activity of these variants would confirm the diagnosis of MPN, opening the door to specific treatment (cytoreductive, JAK2 inhibitor or interferon). It also has an important prognostic value, particularly in the case of MPN, for which life expectancy varies from 5 to 7 years, with terminal progression to acute myeloid leukemia (AML in 15 to 20% of cases) or bone marrow failure. Using a battery of functional assays, this study aims to characterize these variants.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 30
Est. completion date April 2025
Est. primary completion date April 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 99 Years
Eligibility Inclusion Criteria: • Patient with suspected MPN Exclusion Criteria: • Patient with variant of cMPL already described in the literature.

Study Design


Intervention

Other:
Gene sequencing
Next generation sequencing of candidate genes (JAK2, cMPL, CALR, ASXL1 and NF-E2)

Locations

Country Name City State
France CHU de Nîmes Nîmes

Sponsors (1)

Lead Sponsor Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Growth of cultured cells with site-directed mutagenesis of identified variants in the presence of thrombopoietin Thrombopoietin concentration curve Day 0
Primary Ability of cultured cells with site-directed mutagenesis of identified variants to activate the MPL - JAK2 pathway STAT5 Luciferase reporter system Day 0
Primary Ability of cultured cells with site-directed mutagenesis of identified variants to phosphorylate proteins in the MPL - JAK2 pathway Western blot of JAK2, STAT (3 and 5) AKT, ERK1 /2 proteins Day 0
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