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Trial record 2 of 9 for:    XBP1

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

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ClinicalTrials.gov Identifier: NCT02823184
Recruitment Status : Recruiting
First Posted : July 6, 2016
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
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).

Condition or disease Intervention/treatment
Polycythemia Vera Essential Thrombocythemia Biological: RNA sample of total leukocytes before start of 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.

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Endoplasmic Reticulum Stress and Resistance to Treatments in Ph-negative Myeloproliferative Neoplasms
Actual Study Start Date : April 27, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019


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




Primary Outcome Measures :
  1. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Polycythemia Vera or Essential Thrombocythemia
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02823184


Contacts
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Contact: Olivier MANSIER, Doctor 05 56 79 56 79 ext +33 olivier.mansier@gmail.com

Locations
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France
Chu Angers Recruiting
Angers, France
Contact: Françoise BOYER         
Ch de La Cöte Basque Recruiting
Bayonne, France
Contact: Frédéric BAUDUER         
Chu de Bordeaux Recruiting
Bordeaux, France
Contact: Olivier MANSIER         
Crlcc Bergonie Recruiting
Bordeaux, France
Contact: Gabriel ETIENNE         
Chu de Brest Recruiting
Brest, France
Contact: Eric LIPPERT         
Ch de Dax Recruiting
DAX, France
Contact: François Lifermann         
Ch de Libourne Recruiting
Libourne, France
Contact: Didier ADIKO         
Chu de Toulouse Recruiting
Toulouse, France
Contact: Eric DELABESSE         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
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Principal Investigator: Olivier MANSIER, Doctor University Hospital, Bordeaux

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT02823184     History of Changes
Other Study ID Numbers: CHUBX 2014/27
First Posted: July 6, 2016    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital, Bordeaux:
Myeloproliferative neoplasms
Endoplasmic reticulum stress

Additional relevant MeSH terms:
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Neoplasms
Polycythemia
Myeloproliferative Disorders
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Hematologic Diseases
Bone Marrow Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders