Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Myeloproliferative Neoplasm Clinical Trial

— MPN-BIOCLOT  

Official title:

Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04177576
• Other study ID #: CHUBX 2018/50
• Status: Completed
• Start date: February 24, 2020
• Est. completion date: January 26, 2022

Study information

• Verified date: October 2022
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Thrombosis is the main cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPN). However, the pathogenesis of thrombosis in MPN is still largely elusive. Neutrophils can release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". NETs are known to be procoagulant. Our main objective is to quantify NETs biomarkers expression in MPN patients and define if they could be used as prognostic factors in the outcome of thrombosis in these patients.

Description:

Myeloproliferative neoplasms (MPN) are acquired clonal hematopoietic stem cell disorders, characterized by an increase in one or more myeloid lineages. The Philadelphia chromosome negative (Ph-) MPN include polycythemia vera (PV) with an excess of red blood cells, essential thrombocythemia (ET) with an increase in platelets and primary myelofibrosis (PMF). Arterial and venous thromboses are the main causes of morbidity and mortality in MPN with reported incidences ranging from 12-39% in PV and 11-25% in ET. The pathogenesis of thrombosis in MPN patients is complex and still largely elusive. The overproduction of neutrophils could be an important risk factor in the thrombus formation. Indeed neutrophils are known to promote thrombosis when they release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". Increased NETosis has been reported in a mouse model of MPN. The main objective of this study is to investigate whether NET biomarkers are associated with increased thrombotic risk in patients with ET. Indeed, an international thrombotic prognostic score has been published in ET, ie the IPSET Thrombosis score (history of thrombosis, age, presence of JAK2V617F, cardiovascular risk factors).

Plasma from MPN patients will be collected, at the time of diagnosis, and measure markers of neutrophil activation, including NET biomarkers. The IPSET Thrombosis score will be evaluated in patients with ET and the correlation between the IPSET Thrombosis score and these biomarkers will be measured.

No follow-up is required for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: January 26, 2022
• Est. primary completion date: January 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults (age =18 years),

• Patients diagnosed with Polycythemia vera (PV) or essential thrombocythemia (ET) according to WHO 2008 criteria,

• Affiliated to the national social security system,

• Signed informed consent form will be required for each included subject after having read the information note,

• Patient agreeing to be included in the FIMBANK register and having signed the corresponding consent

Exclusion Criteria:

• Adults (age >18 years), male or female,

• Patients treated with heparin or undergoing cytoreductive treatment,

• Pregnant or lactating woman,

• Person under guardianship, tutorship or other legal protection scheme or incapable of giving consent

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Thrombosis

Intervention

Biological:
• 2 additional tubes of blood
2 additional tubes of blood will be collected to prepare plasma aliquots used tomeasure markers of neutrophil activation

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CH Annecy Genevois	Annecy
France	CH Avignon	Avignon
France	CHU Bordeaux, Hématologie Biologique	Bordeaux
France	CHU Bordeaux, Hématologie Clinique et Thérapie Cellulaire	Bordeaux
France	CHU Bordeaux, Médecine Interne	Bordeaux
France	Institut Bergonié	Bordeaux
France	CHRU Brest	Brest
France	CHU Henri Mondor - APHP	Créteil
France	CH Dax	Dax
France	CHU Dijon	Dijon
France	CHU Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	CH Mont de Marsan	Mont-de-Marsan
France	CHU Nancy	Nancy
France	Hôpital Européen Georges Pompidou - APHP	Paris
France	Hôpital Saint-Louis - APHP	Paris
France	CH Perpignan	Perpignan
France	CHU Poitiers	Poitiers
France	CH Rochefort	Rochefort
France	CH Roubaix	Roubaix
France	IUCT-Oncopôle	Toulouse
France	CH Valenciennes	Valenciennes
France	Hôpital Paul Brousse	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between NET biomarkers and the risk of thrombosis	Correlation between NET biomarkers measurated in plasma samples and the risk of thrombosis evaluated by the prognostic score IPSET thrombosis	1 day
Secondary	Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and a history of thrombosis		1 day
Secondary	Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and the subtype of MPN disease (ET or PV)		1 day
Secondary	Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and the presence of JAK2V617F mutation		1 day