Identification of Factors Associated With Treatment Response in Patients With Polycythemia Vera, Essential Thrombocythemia, and Pre-myelofibrosis. (BioPredictor)

First-line treatment for patients with polycythemia vera, essential thrombocythemia, and pre-myelofibrosis is based on hydroxyurea or pegylated interferon. The objective of treatment is to prevent thrombotic complications and leukemic transformation. Despite overall good response rates, some patients do not respond to treatment and others lose their response over time. Both situations are associated with worse survival and there are to date no clear predictive factors for response although the existence of additional mutations seems unfavorable.

In this exploratory study, we hypothesize that biological factors at diagnosis are associated with hematological response at 12 months. We will more specifically study the association between mutational profile, assessed by next-generation sequencing, and cytokine profile with hematological response.

This study will help in identifying patients who will not respond to hydroxyurea or pegylated interferon and give the opportunity to try other treatments upfront, in the perspective of precision medicine. On the basic science side, this study will help in understanding the molecular and immunological factors involved in resistance to treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Myeloproliferative Neoplasm
• Intervention / Treatment: Diagnostic test: Next-generation sequencing

• Study Type: Observational
• Enrollment (Anticipated): 120

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults with polycythemia vera, essential thrombocythemia, or pre-myelofibrosis requiring first-line treatment with hydroxyurea or pegylated interferon.

Description

Inclusion Criteria:

• Adults with polycythemia vera, essential thrombocythemia, or pre-myelofibrosis.
• Indication for first-line treatment with hydroxyurea or pegylated interferon.
• Consent to participate.
• Affiliated to social security.

Exclusion Criteria:

• Previous treatment.
• Other on-going malignancy, including overt myelofibrosis.
• Other treatment such as phlebotomy solely, ruxolitinib, anagrelide, or pipobroman.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete hematological response	ELN-2013 criteria by meeting all of the following: Durable resolution of disease-related signs including palpable hepatosplenomegaly, large symptoms improvement, AND; Durable peripheral blood count remission, defined as: platelet count ≤400 ×109/L, WBC count <10 × 109/L, Ht lower than 45% without phlebotomies (for PV patients), absence of leukoerythroblastosis, AND; Without signs of progressive disease, and absence of any hemorrhagic or thrombotic events.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete hematological response	ELN-2013 criteria by meeting all of the following: Durable resolution of disease-related signs including palpable hepatosplenomegaly, large symptoms improvement, AND; Durable peripheral blood count remission, defined as: platelet count ≤400 ×109/L, WBC count <10 × 109/L, Ht lower than 45% without phlebotomies (for PV patients), absence of leukoerythroblastosis, AND; Without signs of progressive disease, and absence of any hemorrhagic or thrombotic events.	24, 36, 48, and 60 months
Molecular response	ELN-2013 criteria: Complete response is defined as eradication of a preexisting abnormality (CALR, JAK2, or MPL mutations) by quantitative PCR. Partial response applies only to patients with at least 20% mutant allele burden at baseline. Partial response is defined as ≥50% decrease in allele burden by quantitative PCR.	12 and 24 months

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Collaborators: Poitiers University Hospital; University Hospital, Brest; Rennes University Hospital; Nantes University Hospital; University Hospital, Tours

Study record dates

Study Major Dates

• Study Start (Anticipated): September 8, 2022
• Primary Completion (Anticipated): September 7, 2024
• Study Completion (Anticipated): October 4, 2029

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Myeloproliferative Disorders; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: 2022-A01044-39

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No