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

• ClinicalTrials.gov Identifier: NCT05440838
• Recruitment Status: Not yet recruiting
• First Posted: July 1, 2022
• Last Update Posted: July 1, 2022
• Sponsor: University Hospital, Angers
• Collaborators: University Hospital, Brest; Nantes University Hospital; Poitiers University Hospital; Rennes University Hospital; University Hospital, Tours
• Information provided by (Responsible Party): University Hospital, Angers

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Myeloproliferative Neoplasm	Diagnostic Test: Next-generation sequencing

Study Design

• Study Type: Observational
• Estimated Enrollment: 120 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Identification of Factors Associated With Treatment Response in Patients With Polycythemia Vera, Essential Thrombocythemia, and Pre-myelofibrosis.
• Estimated Study Start Date: September 8, 2022
• Estimated Primary Completion Date: September 7, 2024
• Estimated Study Completion Date: October 4, 2029

Groups and Cohorts

Intervention Details:

• Diagnostic Test: Next-generation sequencing
  Next-generation sequencing and cytokine profile will be established in all patients before the start of treatment.
  Other Name: Cytokines

Outcome Measures

Primary Outcome Measures :

1. Complete hematological response [ Time Frame: 12 months ]

   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.

Secondary Outcome Measures :

1. Complete hematological response [ Time Frame: 24, 36, 48, and 60 months ]

   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.
2. Molecular response [ Time Frame: 12 and 24 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: University Hospital, Angers
• ClinicalTrials.gov Identifier: NCT05440838
• Other Study ID Numbers: 2022-A01044-39
• First Posted: July 1, 2022
• Last Update Posted: July 1, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Polycythemia Vera; Primary Myelofibrosis; Myeloproliferative Disorders; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Platelet Disorders; Blood Coagulation Disorders; Hemorrhagic Disorders