Clinical trial NCT02823184: Endoplasmic Reticulum Stress and Resistance to Treatments in Ph-negative Myeloproliferative Neoplasms
Official title: Endoplasmic Reticulum Stress and Resistance to Treatments in Ph-negative Myeloproliferative Neoplasms
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Polycythemia Vera
Essential Thrombocythemia
Keywords: Myeloproliferative neoplasms
Endoplasmic reticulum stress
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2016-07-06
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Polycythemia Vera or Essential Thrombocythemia

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).

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: After 6 months of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Chu Angers
city: Bayonne
country: France
facility: Ch de La Cöte Basque
city: Bordeaux
country: France
facility: Chu de Bordeaux
city: Bordeaux
country: France
facility: Crlcc Bergonie
city: Brest
country: France
facility: Chu de Brest
city: DAX
country: France
facility: Ch de Dax
city: Libourne
country: France
facility: Ch de Libourne
Study officials:
affiliation: University Hospital, Bordeaux
name: Olivier MANSIER, Doctor
role: PRINCIPAL_INVESTIGATOR
References: