Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Blood sampling.
- Who it may be relevant to
- Registry conditions: Myeloproliferative Neoplasm. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Procedure Blood sampling
A specific blood sampling will be performed in addition to the classical evaluations that are performed in routine practice
Primary outcome measures
- History of thrombosis at MPN diagnosis [Time frame: At inclusion]
Secondary outcome measures (8)
- The JAK2V617F allele burden measured in red blood cells [Time frame: At inclusion]
- The JAK2V617F allele burden measured in platelets [Time frame: At inclusion]
- The JAK2V617F allele burden measured in granulocytes [Time frame: At inclusion]
- The presence of the JAK2V617F mutation in endothelial cells [Time frame: At inclusion]
- The clonality profile [Time frame: At inclusion]
- The type of MPN according to the 2016 WHO classification of hematological malignancies [Time frame: At inclusion]
- The IPSET-Thrombosis score [Time frame: At inclusion]
- The type of thrombosis [Time frame: At inclusion]
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 11 centers
- CHU d'Angers, Service Maladies du Sang — Angers
- CH de Bayonne, Service Hématologie Clinique — Bayonne
- CHU de Bordeaux, Service Médecine Interne et Maladies Infectieuses — Bordeaux
- Institut Bergonié, Service Hématologie Clinique — Bordeaux
- CHU de Brest, Service Hématologie Clinique — Brest
- CH de Dax, Service Hématologie Clinique — Dax
- CH de Libourne, Service Hématologie Clinique — Libourne
- CH de Mont de Marsan, Service Oncologie — Mont-de-Marsan
- … and 3 more centers
Identifiers
NCT: NCT05839717 · CHUBX 2022/16