Endoplasmic Reticulum Stress and Resistance to Treatments in Ph-negative Myeloproliferative Neoplasms (PhiNESS)

June 18, 2020 updated by: University Hospital, Bordeaux
The aim of this study is to evaluate the endoplasmic reticulum stress markers as predictive for response to hydroxyurea in polycythemia vera (PV) and essential thrombocythemia (ET).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The recent discovery of calreticulin mutations in myeloproliferative neoplasms point to the unexpected role of the endoplasmic reticulum biology in the pathophysiology in these diseases. Otherwise, the association of endoplasmic reticulum stress with solid cancers, in particular in resistance to chemotherapy, is well documented, contrary to hematological malignancies. The study aims to evaluate endoplasmic reticulum stress markers as predictors for the response to hydroxyurea in polycythemia vera and essential thrombocythemia patients. The main objective is to correlate endoplasmic reticulum stress (defined as splicing of XBP1 above 30%) to the rate of complete response after 6 months according to the 2009 ELN criteria. This is an observational retrospective study.

Study Type

Observational

Enrollment (Actual)

148

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France
        • CHU Angers
      • Bayonne, France
        • CH de la Côte Basque
      • Bordeaux, France
        • CHU de Bordeaux
      • Bordeaux, France
        • Crlcc Bergonie
      • Brest, France
        • CHU de Brest
      • DAX, France
        • CH de Dax
      • Libourne, France
        • CH de Libourne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with Polycythemia Vera or Essential Thrombocythemia

Description

Inclusion Criteria:

  • ET or PV patients diagnosed before acceleration phase and treated by hydroxyurea with a follow up period of at least 6 months following treatment start.

  • Diagnosis criteria of PV :

    • WHO criteria of PV with :

      • Acquired JAK2V617F mutation > 5%
      • Absence of evident cause of secondary polycythemia

  • Diagnosis criteria of ET :

    • Platelet count > 450 G/L
    • Absence of PV or Chronic Myeloid Leukemia
    • Bone marrow biopsy preferred but not necessary in absence of reactional causes (CRP and ferritin levels normal) and/or presence of acquired JAK2V617F, CALR exon 9 or MPL exon 10
  • Availability of RNA sample of total leukocytes before start of treatment.

Exclusion Criteria:

In absence of clonality marker, presence of secondary cause of :

  • Thrombocytosis :

    • Inflammatory syndrom (CRP or SV increased)
    • Iron deficiency (decreased ferritin level or increased soluble transferrin receptor level)

  • Polycythemia :

    • Increased or normal level of EPO in context of :

      • Hypoxia, respiratory insufficiency
      • Sleep apnea syndrome
      • Hyperaffin hemoglobin
  • Absence of treatment by hydroxyurea
  • Treatment by anagrelide, P32, pipobroman, interferon without subsequent hydroxyurea treatment.
  • Concommitant treatment by other cancer chemotherapy (in a context of solid cancer for example).
  • Diagnostic during transformation to acute leukemia
  • Treatment by hydroxyurea during less than 6 months
  • Bad observance of the cytotoxic treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients
ET or PV patients diagnosed before acceleration phase and treated by hydroxyurea with a follow up period of at least 6 months following treatment start, with a RNA sample of total leukocytes before start of treatment available
Biological: RNA sample of total leukocytes before start of treatment
RNA sample of total leukocytes before start of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To correlate endoplasmic reticulum stress (defined as splicing of XBP1 above 30%) to the rate of complete response after 6 months according to the 2009 ELN criteria
Time Frame: After 6 months of treatment
After 6 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Olivier MANSIER, Doctor, University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2017

Primary Completion (Actual)

April 27, 2019

Study Completion (Actual)

April 27, 2019

Study Registration Dates

First Submitted

June 24, 2016

First Submitted That Met QC Criteria

July 5, 2016

First Posted (Estimate)

July 6, 2016

Study Record Updates

Last Update Posted (Actual)

June 19, 2020

Last Update Submitted That Met QC Criteria

June 18, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2014/27

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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