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

Myeloproliferative Neoplasm Clinical Trial

— CALRSUIVI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04942080
• Other study ID #: 49RC21_0156
• Status: Recruiting
• Phase: N/A
• Start date: October 28, 2021
• Est. completion date: April 28, 2026

Study information

• Verified date: November 2022
• Source: University Hospital, Angers
• Contact: Laurane COTTIN, Doctor
• Phone: +33 2 41 35 53 53
• Email: Laurane.Cottin[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: April 28, 2026
• Est. primary completion date: April 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Primary Myelofibrosis
• Primary Myelofibrosis, Fibrotic Stage
• Primary Myelofibrosis, Prefibrotic Stage
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Biological:
• CALR allele burden quantification
DNA extraction from blood sample for CALR mutation quantification (fragment analysis) at diagnosis and follow-up (inclusion period: 3 years) max 1 sample/year secondary outcome: mutational landscape by Next Generation Sequencing (NGS) analysis at diagnosis

Locations

Country	Name	City	State
France	CHU Angers	Angers

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Angers	Ligue contre le cancer, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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-Roué I, Martin A, Sadot-Lebouvier S, Delneste Y, Chrétien 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	3 years follow-up
Secondary	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