Clinical trial NCT04942080: Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)
Official title: Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Myeloproliferative Neoplasm
Essential Thrombocythemia
Primary Myelofibrosis, Prefibrotic Stage
Primary Myelofibrosis, Fibrotic Stage
Keywords: CALR
Myeloproliferative Neoplasm
Essential Thrombocythemia
Primary Myelofibrosis
Thrombocytosis
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Ligue contre le cancer, France
First posted: 2021-06-28
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Prospective study to evaluate the relevance of CALR allele burden monitoring as a molecular marker of disease progression.

Detailed description: A first local study on 45 patients showed the prognostic impact of CALR mutation quantification in follow-up, independently of the European LeukemiaNet (ELN) prognostic score validated in this group of patients.

This study aims to evaluate a multicenter cohort of 260 patients, including all types of CALR-mutated MPNs and several follow-up samples, to model the temporal evolution of CALR allele burden.

Blood of MPN patients will be collected, at the time of diagnosis and for 3 years (max 1 sample/year), for the quantification of the CALR allele burden. During follow-up, a clinicobiological score to define the progression or not of the disease for each patient will be evaluated in Essential Thrombocythemia (ET) and MyeloFibrosis (MF).

Eligibility criteria: Inclusion Criteria:

* adults (age ≥18 years),
* affiliated to the national social security system,
* with CALR mutated myeloproliferative neoplasm diagnosed between 2006 - 2020,
* for which at least one sample is available at the time of diagnosis or before cytoreductive treatment,
* who signed the consent to participate in the study,
* included, or consenting to be included, in the national clinical-biological database of France Intergroupe Syndrome Myéloprolifératifs (FIM).

Exclusion Criteria:

* patient with another active hematological disease or cancer at the time of diagnosis,
* person subject to legal protection scheme or incapable of giving consent.

Primary outcomes:
measure: For each disease, Hazard Ratio of the different trajectories of CALR allele burden to explain the time to onset of disease progression by the clinicobiological score.
timeFrame: 3 years follow-up
Secondary outcomes:
measure: A multinomial logistic model will be performed to identify the characteristics associated with the different trajectories of CALR allele burden (pathology, treatment, additional mutations, type of CALR mutation).
timeFrame: 3 years follow-up
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
Study officials:
References:
citation: Cottin L, Riou J, Orvain C, Ianotto JC, Boyer F, Renard M, Truchan-Graczyk M, Murati A, Jouanneau-Courville R, Allangba O, Mansier O, Burroni B, Rousselet MC, Quintin-Roue I, Martin A, Sadot-Lebouvier S, Delneste Y, Chretien JM, Hunault-Berger M, Blanchet O, Lippert E, Ugo V, Luque Paz D. Sequential mutational evaluation of CALR -mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression. Br J Haematol. 2020 Mar;188(6):935-944. doi: 10.1111/bjh.16276. Epub 2019 Nov 11.