Ignite Creation Date:
2025-12-26 @ 3:59 PM
Ignite Modification Date:
2025-12-26 @ 3:59 PM
Study NCT ID:
NCT06246006
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-02-07
First Post:
2024-01-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009196', 'term': 'Myeloproliferative Disorders'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D013922', 'term': 'Thrombocytosis'}], 'ancestors': [{'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D001791', 'term': 'Blood Platelet Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001483', 'term': 'Base Sequence'}], 'ancestors': [{'id': 'D015394', 'term': 'Molecular Structure'}, {'id': 'D001669', 'term': 'Biochemical Phenomena'}, {'id': 'D055598', 'term': 'Chemical Phenomena'}, {'id': 'D040342', 'term': 'Genetic Structures'}, {'id': 'D055614', 'term': 'Genetic Phenomena'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples and bone marrow samples will be taken depending on the clinical management of the patient'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2023-10-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-01', 'completionDateStruct': {'date': '2025-04', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-01-30', 'studyFirstSubmitDate': '2024-01-30', 'studyFirstSubmitQcDate': '2024-01-30', 'lastUpdatePostDateStruct': {'date': '2024-02-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-02-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-04', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Growth of cultured cells with site-directed mutagenesis of identified variants in the presence of thrombopoietin', 'timeFrame': 'Day 0', 'description': 'Thrombopoietin concentration curve'}, {'measure': 'Ability of cultured cells with site-directed mutagenesis of identified variants to activate the MPL - JAK2 pathway', 'timeFrame': 'Day 0', 'description': 'STAT5 Luciferase reporter system'}, {'measure': 'Ability of cultured cells with site-directed mutagenesis of identified variants to phosphorylate proteins in the MPL - JAK2 pathway', 'timeFrame': 'Day 0', 'description': 'Western blot of JAK2, STAT (3 and 5) AKT, ERK1 /2 proteins'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['leukemia', 'neoplasm', 'polymorphism', 'thrombocythemia', 'Thrombopoietin receptor,'], 'conditions': ['Myeloproliferative Disorder']}, 'descriptionModule': {'briefSummary': '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.\n\nNext 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.\n\nUsing a battery of functional assays, this study aims to characterize these variants.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patient with suspected MPN screened at CHU Nîmes', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n• Patient with suspected MPN\n\nExclusion Criteria:\n\n• Patient with variant of cMPL already described in the literature.'}, 'identificationModule': {'nctId': 'NCT06246006', 'acronym': 'MPL - NPM', 'briefTitle': 'Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia', 'organization': {'class': 'OTHER', 'fullName': 'Centre Hospitalier Universitaire de Nīmes'}, 'officialTitle': 'Functional Characterization of Thrombopoietin/cMPL Receptor Mutations in Myeloproliferative Neoplasia', 'orgStudyIdInfo': {'id': 'NIMAO/2023-1/SC01'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Patients with suspected MPN', 'interventionNames': ['Other: Gene sequencing']}], 'interventions': [{'name': 'Gene sequencing', 'type': 'OTHER', 'description': 'Next generation sequencing of candidate genes (JAK2, cMPL, CALR, ASXL1 and NF-E2)', 'armGroupLabels': ['Patients with suspected MPN']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Nîmes', 'country': 'France', 'facility': 'CHU de Nîmes', 'geoPoint': {'lat': 43.83665, 'lon': 4.35788}}], 'overallOfficials': [{'name': 'Serge Carillo', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'CHU de Nimes'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centre Hospitalier Universitaire de Nīmes', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}