Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05839717

Collaborator

(none)

120

Enrollment

Locations

Anticipated Duration (Months)

10.9

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Myeloproliferative Neoplasms (MPN) are associated with an increased risk of thrombosis. Platelets, red blood cells (RBC), leukocytes and endothelial cells are involved in these complications. An association with the JAK2V617F allele burden assessed in leukocytes has also been suggested. In some patients the allele burden measured in platelets and red blood cells is higher than the one determined in leukocytes. Our project aims at associating the risk of thrombosis with the allele burden determined in the cell populations (platelets, red blood cells, granulocytes and endothelial cells) and identifying high-risk clonality profiles.

Condition or Disease	Intervention/Treatment	Phase
Myeloproliferative Neoplasm	Procedure: Blood sampling

Detailed Description

Myeloproliferative Neoplasms (MPN) are hematological malignancies associated with an increased risk of thrombosis. Although different cell types have been involved in these complications (platelets, red blood cells, leucocytes and endothelial cells), there do not exist any reliable biomarker to predict the thrombotic risk in MPN patients. While some studies suggested that the JAK2V617F allele burden measured in leukocytes was associated with the risk of thrombosis, other studies did not confirm these results. Besides, a recent work demonstrated that in some patients, the JAK2V617F allele burden measured in platelets and red blood cells was higher than the one determined in leukocytes. Moreover, some patients present JAK2V617F mutated endothelial cells, known as pro-thrombotic in in vitro and animal models. The CLOJAK project will search for an association between the thrombotic risk in MPN and the proportion of cells carrying the JAK2V617F mutation in erythroid cells and platelets or its presence in endothelial cells. The objective is to determine a clonality profile (i.e. the profile of repartition of the JAK2V617F allele burden in the different hematopoietic and endothelial lineages) associated with the occurrence of thrombosis in MPN patients.

One hundred and twenty PV and ET patients will be studied at diagnosis. Their platelets, red blood cells, granulocytes and endothelial cells will be isolated. The JAK2V617F allele burden will be measured in these cells thanks to a digital PCR technic. An association between the clonality profile and the existence of a thrombosis at diagnosis, the MPN phenotype (PV or ET), the IPSET-thrombosis score and the type of thrombosis (venous, arterial, splanchnic) will be searched.

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
PV and ET patients The cohort will be composed of PV and ET patients, some with a history of thrombosis and some without any history of thrombosis. A comparison will also be performed between patients with different MPN (PV or ET) and the type of thrombosis (venous, arterial, splanchnic)	Procedure: Blood sampling A specific blood sampling will be performed in addition to the classical evaluations that are performed in routine practice

Arm

Intervention/Treatment

PV and ET patients

The cohort will be composed of PV and ET patients, some with a history of thrombosis and some without any history of thrombosis. A comparison will also be performed between patients with different MPN (PV or ET) and the type of thrombosis (venous, arterial, splanchnic)

Procedure: Blood sampling

A specific blood sampling will be performed in addition to the classical evaluations that are performed in routine practice

Outcome Measures

Primary Outcome Measures

History of thrombosis at MPN diagnosis [At inclusion]
History of thrombosis at MPN diagnosis defined as the occurrence of a venous (deep vein thrombosis, pulmonary embolism) or arterial thrombosis (ischemic stroke or myocardial infarction) or a thrombosis in the splanchnic area

Secondary Outcome Measures

The JAK2V617F allele burden measured in red blood cells [At inclusion]
The JAK2V617F allele burden measured in platelets [At inclusion]
The JAK2V617F allele burden measured in granulocytes [At inclusion]
The presence of the JAK2V617F mutation in endothelial cells [At inclusion]
The clonality profile [At inclusion]
The clonality profile defined based on the association of cell lineages in which a JAK2V617F allele burden over 25% is measured together with the detection (or not) of the JAK2V617F mutation in endothelial cells
The type of MPN according to the 2016 WHO classification of hematological malignancies [At inclusion]
The IPSET-Thrombosis score [At inclusion]
The type of thrombosis [At inclusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patient (age ≥ 18 years)
Inclusion at diagnosis or during the year following the diagnosis of PV or ET (2016 WHO criteria except bone marrow biopsy that is optional), before introduction of a cytoreductive treatment
Patient carrying a JAK2V617F mutation
Subject registered with a social security scheme
Written informed consent obtained
Acceptance of inclusion in the FIMBANK registry (specific consent form needed)

Exclusion Criteria:

ET or PV Patient not carrying a JAK2V617F mutation
Patient with cytoreductive treatment (hydroxyurea, anagrelide, interferon, ruxolitinib or other chemotherapy) at the time of blood sampling
Person under judicial safeguards, trustee or curatorship
Person unable to give her consent
Non-cooperative person
Exclusion period after another clinical study or participation to another clinical study in the 30 days before inclusion

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU d'Angers, Service Maladies du Sang	Angers	France	49933
2	CH de Bayonne, Service Hématologie Clinique	Bayonne	France	64100
3	CHU de Bordeaux, Service Médecine Interne et Maladies Infectieuses	Bordeaux	France	33000
4	Institut Bergonié, Service Hématologie Clinique	Bordeaux	France	33000
5	CHU de Brest, Service Hématologie Clinique	Brest	France	29609
6	CH de Dax, Service Hématologie Clinique	Dax	France	40100
7	CH de Libourne, Service Hématologie Clinique	Libourne	France	33500
8	CH de Mont de Marsan, Service Oncologie	Mont-de-Marsan	France	40000
9	CHU de Bordeaux, Service Hématologie Biologie	Pessac	France	33604
10	CHU de Bordeaux, Service Hématologie Clinique et Thérapie Cellulaire	Pessac	France	33604
11	CHU de Bordeaux, Service Médecine Interne	Pessac	France	33604