Interest of CALR Allele Burden in Diagnosis and Follow-up of Patients With CALR Mutated Myeloproliferative Syndromes (CALRSUIVI)

Not Applicable

Recruiting

• Conditions: Primary Myelofibrosis, Prefibrotic Stage; Myeloproliferative Neoplasm; Essential Thrombocythemia; Primary Myelofibrosis, Fibrotic Stage
• Interventions: Biological: CALR allele burden quantification

• Registration Number: NCT04942080
• Lead Sponsor: University Hospital, Angers

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).

Study Timeline

• Study First Submitted: 2021-06-09
• Study First Submitted QC: 2021-06-18
• Study First Posted: 2021-06-28
• Study Start: 2021-10-28
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-02
• Last Update Posted: 2022-11-03
• Primary Completion: 2023-04-28
• Study Completion: 2026-04-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 260

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CALRSUIVI cohort	CALR allele burden quantification	-

Primary Outcome Measures

Name	Time	Method
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.	3 years follow-up	Clinicobiological score : For ET, disease progression if ≥ 1 of: * leukocytosis \> 12 G/L or myelemia \> 10% or erythroblasts \> 1%,; * anemia or thrombocytopenia not related to drug toxicity,; * development or worsening of splenomegaly,; * development of thrombocytosis (platelets \> 450 G/L) on cytoreductive therapy,; * poor disease control (at least one change in therapy for reasons other than adverse events),; * hematologic transformation or death related to hematologic pathology.; For MF, disease progression if ≥ 1 of: * anemia \< 100 g/L, neutropenia \< 1 G/L, thrombocytopenia \< 100 G/L and/or development of general signs not previously present or recurring after improvement,; * increase in leukocytosis \> 25 G/L not previously present,; * appearance or aggravation of transfusion dependence,; * appearance (\> 5 cm) or aggravation (\> 50%) of splenomegaly,; * leukemic transformation or death related to the hematologic pathology.

Secondary Outcome Measures

Name	Time	Method
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).	3 years follow-up

Trial Locations

Locations (1)

CHU Angers; 🇫🇷 Angers, France