- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05419648
Role of Monocytes Sub-populations in Thrombosis Associated With Myeloproliferative Neoplasms (MonSThr) (MonSThr)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by an increased risk of thrombosis, in particular in Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Predicting the risk of thrombosis in PV and ET patients helps at determining their care (use of antiaggregant and cytoreductive therapies), but relies only on limited clinical and biological criteria (age over 60 years, history of thrombosis, presence of the JAK2V617F mutation, presence of cardiovascular risk factors). Monocytes sub-populations could represent a new biomarker of thrombotic risk in PV and ET patients. Indeed, it has been shown that monocytes are activated and exhibit pro-thrombotic properties in MPN patients, especially those with a history of thrombosis. Some studies have suggested the CD16+ monocytes (intermediate and non-classical monocytes) are associated with an increased risk of arterial thrombosis. Because these monocytes are observed in inflammatory contexts, and because MPN are associated with a chronic inflammation, MPN could be associated with an increase of the proportion or the absolute count of CD16+ monocytes that could be involved in thrombotic complications observed in PV and ET patients.
In this project, an association between the proportion of CD16+ monocytes and thrombosis in PV and ET patients will be searched. Monocytes sub-populations will be studied in PV and ET patients at diagnosis as described by Selimoglu-Buet et al.1 The proportion of CD16+ (intermediate + non-classical) monocytes will be compared between patients presenting with a history of thrombosis and those without any history of thrombosis. The association between the absolute count and the proportion of CD16+, intermediate and non-classical monocytes and the occurrence of thrombosis before diagnosis, the MPN phenotype, the driver mutation, the allelic burden, the clinico-biological presentation and the existence of an inflammatory state will also be evaluated. Due to the low frequency and the high latency of thrombosis reoccurrence, patients' samples only at diagnosis (or during the year after diagnosis) will be analyzed and an association with a history of thrombosis will be made.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Olivier MANSIER
- Phone Number: +33 05 56 79 56 79 (poste 74601)
- Email: olivier.mansier@chu-bordeaux.fr
Study Contact Backup
- Name: Chloé JAMES
- Phone Number: +33 05 57 65 64 78
- Email: chloe.james@chu-bordeaux.fr
Study Locations
-
-
-
Bordeaux, France
- Recruiting
- CHU de Bordeaux, Hématologie clinique et thérapie cellulaire
-
Contact:
- Clémence MEDIAVILLA
- Email: clemence.mediavilla@chu-bordeaux.fr
-
Bordeaux, France
- Recruiting
- CHU de Bordeaux, Laboratoire Hématologie
-
Contact:
- Olivier MANSIER
- Email: olivier.mansier@chu-bordeaux.fr
-
Bordeaux, France
- Recruiting
- CHU de Bordeaux, Médecine interne et immunologie clinique
-
Contact:
- Pierre DUFFAU
- Email: pierre.duffau@chu-bordeaux.fr
-
Bordeaux, France
- Recruiting
- CHU de Bordeaux, Médecine Interne et maladies infectieuses
-
Contact:
- Jean-François VIALLARD
- Email: jean-francois.viallard@chu-bordeaux.fr
-
Bordeaux, France
- Recruiting
- Institut Begonié, Hématologie clinique
-
Contact:
- Etienne GABRIEL
- Email: G.Etienne@bordeaux.unicancer.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adults patients (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 in the presence of a marker of clonality)
- Subject registered with a social security scheme
- Written informed consent obtained
Exclusion Criteria:
- Patients with cytoreductive treatment (hydroxyurea, anagrelide, interferon, ruxolitinib) at the time of blood sampling
- Chronic inflammatory disease (cancer, vasculitis, rheumatism, hepato-gastro-intestinal diseases).
Long term anti-inflammatory treatments:
- Corticoids
- Nonsteroidal anti-inflammatory drugs
- Aspirin (> 325 mg per day)
- Cyclo-oxygenase II inhibitors
- Persons 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
PV and ET patients
For the main objective, 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 different driver mutation (JAK2V617F, JAK2 exon 12, CALR, MPL or absence of such mutations)
|
For all the patients included, a specific blood sampling will be performed in addition to the classical evaluations that are performed in routine practice
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
History of thrombosis
Time Frame: At inclusion, up to 1 year after diagnosis
|
Patients wil be classified as having a history of thrombosis if they had a deep vein thrombosis, pulmonary embolism, splanchnic thombosis or any other significant thrombosis.
Tinnitus, vertigo, headaches, erythromelalgia as well as superficial vein thrombosis will not be considered as thrombotic events
|
At inclusion, up to 1 year after diagnosis
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of CD16+ monocytes in PV and ET patients
Time Frame: At inclusion, up to 1 year after diagnosis
|
The proportion of CD16+ monocytes will be assessed in PV and ET patients, and compared between patients with a history of thrombosis and those without any history of thrombosis
|
At inclusion, up to 1 year after diagnosis
|
Proportion of monocytes sub-populations
Time Frame: At inclusion, up to 1 year after diagnosis
|
The different sub-populations will be defined according to the expression profile of CD14 and CD16, defining classical monocytes (CD14++CD16-), non-classical monocytes (CD14loCD16++) and intermediate monocytes (CD14+CD16+).
The proportion of these sub-populations will be assessed in PV and ET patients, and compared between patients with a history of thrombosis and those without any history of thrombosis
|
At inclusion, up to 1 year after diagnosis
|
Count of monocytes sub-populations
Time Frame: At inclusion, up to 1 year after diagnosis
|
The count (G/L) of the different monocytes sub-populations, ie CD16+ monocytes, classical monocytes (CD14++CD16-), non-classical monocytes (CD14loCD16++) and intermediate monocytes (CD14+CD16+) will be assessed in PV and ET patients, and compared between patients with a history of thrombosis and those without any history of thrombosis
|
At inclusion, up to 1 year after diagnosis
|
Type of MPN
Time Frame: At inclusion, up to 1 year after diagnosis
|
The type of MPN will be determined according to the WHO criteria as PV or ET. Patients will be classified as PV if they have an increased hemoglobin level (>16.5g/dL for men, >16g/dL for women), hematocrit (>49% for men, >48% for women), or red cell mass (>125% of theoretical value), together with a mutation in the JAK2 gene (JAK2V617F or exon 12), and a subnormal EPO level. If performed, bone marrow biopsy should be in favor of an MPN. Patients will be classified as ET if they present a thrombocytosis > 450 G/L, with a detectable mutation in JAK2, CALR or MPL. If performed, bone marrow biopsy should be in favor of an MPN. |
At inclusion, up to 1 year after diagnosis
|
Driver mutation of MPN
Time Frame: At inclusion, up to 1 year after diagnosis
|
At diagnosis, a driver mutation is searched in MPN patients.
We will classify patients in different groups depending on whether they carry the JAK2V617F mutation, a mutation in JAK2 exon 12, a mutation in CALR exon 9, a mutation in MPL exon 10 or any of these mutations (triple negative category).
We will thus distinguish 5 groups of patients: "JAK2V617F", "JAK2 exon 12", "CALR exon 9", "MPL exon 10", "triple negative".
The proportion of monocytes sub-populations will be compared between these different groups of patients
|
At inclusion, up to 1 year after diagnosis
|
Hemoglobin level
Time Frame: At inclusion, up to 1 year after diagnosis
|
A correlation between the hemoglobin level (g/dL) and monocytes sub-populations proportion will be searched
|
At inclusion, up to 1 year after diagnosis
|
Platelets level
Time Frame: At inclusion, up to 1 year after diagnosis
|
A correlation between the platelets level (G/L) and monocytes sub-populations proportion will be searched
|
At inclusion, up to 1 year after diagnosis
|
Leukocytes level
Time Frame: At inclusion, up to 1 year after diagnosis
|
A correlation between the leukocytes level (G/L) and monocytes sub-populations proportion will be searched
|
At inclusion, up to 1 year after diagnosis
|
Thrombosis risk factors
Time Frame: At inclusion, up to 1 year after diagnosis
|
A correlation between the proportion or count of monocytes sub-populations and thrombosis risk factors will be searched.
These include age>60 years, history of thrombosis, tobaccoe use (actual or stopped for les than 3 years), hyperLDLcholesterol level (LDL-Cholesterol > 3,36 mmol/L), hypoHDLcholesterol level (HDL < 1,03 mmol/L in men or < 1,29 mmol/L in women), diabetes (glycemia > 6,93 mmol/L), high blood pressure (> 140/90 mmHg)
|
At inclusion, up to 1 year after diagnosis
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Olivier MANSIER, University Hospital, Bordeaux
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHUBX 2021/29
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myeloproliferative Neoplasm
-
Sociedad de Lucha Contra el Cáncer del EcuadorCompletedMyeloproliferative Disorders | Myeloproliferative Neoplasm | Myeloproliferative Syndrome | Myeloproliferative Neoplasm, Unclassifiable | Myeloproliferative Disease, Not ClassifiedEcuador
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedSotatercept in Treating Patients With Myeloproliferative Neoplasm-Associated Myelofibrosis or AnemiaAnemia | Myelofibrosis | Myelodysplastic/Myeloproliferative NeoplasmUnited States
-
Mayo ClinicNational Cancer Institute (NCI)TerminatedMyelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis, Not Otherwise Specified | Myelodysplastic/Myeloproliferative Neoplasm, Not Otherwise SpecifiedUnited States
-
Astex Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Myeloproliferative Neoplasm | Myelodysplastic/Myeloproliferative NeoplasmUnited States, Canada
-
ImmunoGen, Inc.Active, not recruitingBlastic Plasmacytoid Dendritic Cell Neoplasm | Myeloproliferative NeoplasmUnited States, Spain, Germany, Italy, France, United Kingdom
-
Fred Hutchinson Cancer CenterImmunoGen, Inc.RecruitingAcute Myeloid Leukemia | Myelodysplastic Syndrome | Myeloproliferative Neoplasm | Myelodysplastic/Myeloproliferative Neoplasm | Mixed Phenotype Acute LeukemiaUnited States
-
BeiGeneRecruitingAcute Myeloid Leukemia | Myelodysplastic Syndromes | Myelodysplastic/Myeloproliferative NeoplasmChina, United States, Australia, Spain, Korea, Republic of, New Zealand, Germany
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAcute Myeloid Leukemia | Myelodysplastic Syndrome | Myeloproliferative Neoplasm | Myelodysplastic/Myeloproliferative NeoplasmUnited States
-
AUSL Romagna RiminiCompleted
-
University of California, IrvineCompletedMyeloproliferative NeoplasmUnited States
Clinical Trials on 1 additional tube of blood
-
Centre Hospitalier Universitaire de NiceCompleted
-
University Hospital, LimogesTerminated
-
University Hospital, MontpellierCBS; MICALISRecruitingCancer | ProstateFrance
-
University Hospital, BordeauxCompletedMyeloproliferative NeoplasmFrance
-
Centre Hospitalier Universitaire de BesanconCompleted
-
Centre Hospitalier Universitaire de BesanconUnknown
-
Centre Hospitalier Universitaire de NiceRecruitingNew Coronavirus Disease (COVID-19), Infection With SARS-CoV-2France
-
Hasselt UniversityZiekenhuis Oost-LimburgCompleted
-
Centre Hospitalier Universitaire de BesanconCompleted
-
CHU de ReimsCompletedDosage of Serum Tryptase Levels in a Population of Premature Newborns to Evaluate Mast Cell ActivityPremature NewbornsFrance