Clinical trial NCT05839717: Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)
Official title: Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myeloproliferative Neoplasm
Keywords: Myeloproliferative Neoplasms
Thrombosis
Clonality
JAK2V617F
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2023-05-03
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with Myeloproliferative Neoplasms (MPN) carrying a JAK2V617F mutation

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: History of thrombosis at MPN diagnosis
timeFrame: At inclusion
Secondary outcomes:
measure: The JAK2V617F allele burden measured in red blood cells
timeFrame: At inclusion
measure: The JAK2V617F allele burden measured in platelets
timeFrame: At inclusion
measure: The JAK2V617F allele burden measured in granulocytes
timeFrame: At inclusion
measure: The presence of the JAK2V617F mutation in endothelial cells
timeFrame: At inclusion
measure: The clonality profile
timeFrame: At inclusion
measure: The type of MPN according to the 2016 WHO classification of hematological malignancies
timeFrame: At inclusion
measure: The IPSET-Thrombosis score
timeFrame: At inclusion
measure: The type of thrombosis
timeFrame: At inclusion
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers, Service Maladies du Sang
city: Bayonne
country: France
facility: CH de Bayonne, Service Hématologie Clinique
city: Bordeaux
country: France
facility: CHU de Bordeaux, Service Médecine Interne et Maladies Infectieuses
city: Bordeaux
country: France
facility: Institut Bergonié, Service Hématologie Clinique
city: Brest
country: France
facility: CHU de Brest, Service Hématologie Clinique
city: Dax
country: France
facility: CH de Dax, Service Hématologie Clinique
city: Libourne
country: France
facility: CH de Libourne, Service Hématologie Clinique
city: Mont-de-Marsan
country: France
facility: CH de Mont de Marsan, Service Oncologie
city: Pessac
country: France
facility: CHU de Bordeaux, Service Hématologie Biologie
city: Pessac
country: France
facility: CHU de Bordeaux, Service Hématologie Clinique et Thérapie Cellulaire
city: Pessac
country: France
facility: CHU de Bordeaux, Service Médecine Interne
Study officials:
References: