NCT06923670

Brief Summary

Philadelphia-negative myeloproliferative neoplasms (MPNs) occur sporadically and are due to somatic mutations in the JAK2 (Janus kinase 2), CALR (calreticulin) and MPL (thrombopoietin receptor) genes. However, data from epidemiological and family studies clearly highlight a heritable component that influences the risk of developing MPN and potentially contributes to the observed phenotypic pleiotropy. Genome-wide association studies in MPN familial clusters have identified a number of germline genetic variants associated with an increased risk of developing MPN. The strongest association discovered so far is the presence of the JAK2 46/1 haplotype and, subsequently, several studies have found additional variants in other genes, particularly in the TERT gene. The aim of the study would be to investigate the presence of germline mutations in MPN patients selected on the basis of a family history of myeloid neoplasms through the analysis of both already recognized genes and other potentially implicated ones.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
496

participants targeted

Target at P75+ for not_applicable

Timeline
24mo left

Started May 2025

Typical duration for not_applicable

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress33%
May 2025May 2028

First Submitted

Initial submission to the registry

March 26, 2025

Completed
16 days until next milestone

First Posted

Study publicly available on registry

April 11, 2025

Completed
1 month until next milestone

Study Start

First participant enrolled

May 21, 2025

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2028

Last Updated

May 15, 2025

Status Verified

May 1, 2025

Enrollment Period

2.9 years

First QC Date

March 26, 2025

Last Update Submit

May 14, 2025

Conditions

Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Outcome Measures

Primary Outcomes (2)

  • Comparison between clinical characteristis in patients with and without family history:

    Complete blood count test Presence of splenomegaly Presence of Fibrosis at bone marrow biopsy

    30 months

  • Comparison between biological characteristis in patients with and without family history:

    Presence of driver mutations: JAK2 V617F Calreticulin mutations MPL mutations Presence of detrimental mutations in the following genes: ASXL1, ZSFR2, IDH1, IDH2, EZH2, TP53

    30 months

Secondary Outcomes (2)

  • Prevalence of germline mutations in MPN patients

    36 months

  • Distribution of hematologic malignancies in the group with familial hystory

    36

Study Arms (2)

Patients with familial history of hematological malignancies

EXPERIMENTAL

The investigators will evaluate the presence of mutations in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2

Diagnostic Test: NGS testingDiagnostic Test: NGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Patients without familial history of hematological malignancies

ACTIVE COMPARATOR

The investigators will evaluate the presence of mutations in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2

Diagnostic Test: NGS testingDiagnostic Test: NGS analysis for mutations in genes involved in familial predisposition to hematological malignancies

Interventions

NGS testingDIAGNOSTIC_TEST

The investigators will test in NGS the presence of mutations in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2

Patients with familial history of hematological malignanciesPatients without familial history of hematological malignancies
NGS analysis for mutations in genes involved in familial predisposition to hematological malignanciesDIAGNOSTIC_TEST

The investigators will evaluate the presence of mutations in the following genes: ABRAXAS1, ACD, ANKRD26, APC, ATG2B, ATM, BARD1, BMPR1A, BRCA1/2, BRIP1, CDH1, CDKN2A, CEBPA, CHECK2, CSF3R, DDX41, EPCAM, ERCC6L2, ETV6, FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCL, GATA2, GSKIP, MBD4, MECOM, MEN1, MLH1, MLH3, MRE11, MSH2, MSH6, MUTYH, NBN, NF1, NF2, PALB2, PIK3CA, POLD1, POLE, PMS2, PMS2CL, PTEN, PTPN11, RAD50, RAD51C, RAD51D, RET, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SRP72, STK11, TERC, TERT, TP53, TSC1, TSC2, VHL, WAS, XRCC2

Patients with familial history of hematological malignanciesPatients without familial history of hematological malignancies

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \*Patients \>18 years
  • Diagnosis of MPN (Essential Thrombocythemia, Polycythemia Vera, Myelofibrosis) confirmed according to ICC 2022 criteria
  • Familiarity for myeloid neoplasia: at least one first or second degree relative affected by myeloid neoplasia (probands) OR presence of matching criteria with a proband (controls). Each center will be able to contribute with its own available patients/relatives, providing the clinical-laboratory data required by the study.
  • Signing of informed consent according to ICH/EU/GCP and local national laws (if applicable)

You may not qualify if:

  • Patients \<18 years Patients with other hematological diagnoses; • Lack of informed consen

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Polycythemia VeraThrombocythemia, EssentialPrimary Myelofibrosis

Interventions

Mutation

Condition Hierarchy (Ancestors)

Bone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteNeoplasmsBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesMyeloproliferative DisordersBlood Coagulation DisordersThrombocytosisBlood Platelet DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Genetic VariationGenetic Phenomena

Central Study Contacts

Patrizia chiusolo, MD

CONTACT

393355267999patrizia.chiusolo@unicatt.it

Denise Soldati, Data Manager

CONTACT

390630154206denise.soldati@policlinicogemelli.it

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

March 26, 2025

First Posted

April 11, 2025

Study Start

May 21, 2025

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2028

Last Updated

May 15, 2025

Record last verified: 2025-05