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High Risk Myelodysplasia Treated by Azacytidine : Genetic and Epigenetic (MYRAGE)

Not Applicable
Conditions
High-risk Myelodysplastic Syndromes With Excess Blasts
Interventions
Diagnostic Test: Myelogram
Registration Number
NCT03217903
Lead Sponsor
Central Hospital, Nancy, France
Brief Summary

Myelodysplastic syndromes (MDS) are the most frequent myeloid neoplasms in Western Countries.They mainly affect patients aged 65 years or older. This is a very heterogenous group of diseases, which prognosis is evaluated with International Prognosis Scoring System. High risk MDS present with high frequency of transformation into acute myeloid leukemia. Treatment of high risk MDS often is based on hypomethylating agents, such as 5'-azacytidine (Azacytidine), with a complete response in approximativel 20% of cases..

This treatment is based on 4-week cycles, with daily injection during the first week and rest during the 3 next weeks of the cycle.

Azacytidine efficacy is commonly evaluated with clinical and biological parameters determined by the International Working Group 2006. These parameters are usually evaluated after at least 6 cycles of treatments.

There is a response with Azacytidine treatment in 60% of cases, including 40% of partial responses and 20% of complete responses. In 40% of patients, there is no response, which means that the disases is stable or in progression under therapy.

In this regard, early evaluation of treatment response is an issue. We want to improve our knowledge about early response criteria in Azacytidine-treated high-risk MDS, focusing on SMD with excess blasts, which represent 30 to 40% of total MDS.

Then, the investigator team want to compare DNA methylation profile at diagnosis and after 3 cycles of Azacytidine treatment.

Main objective :

Identify DNA methylation profiles related to response to Azacytidine therapy, after only 3 cycles of treatment, in high risk MDS with excess blasts.

Secondary objective :

Identify at diagnosis DNA methylation profiles that are predicitive of response to Azacytidin, in high risk MDS with excess blasts.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
32
Inclusion Criteria
  • patient benefiting from social welfcare
  • patient followed at the University Hospital of Nancy
  • patient aged 18 years or older
  • patient informed on research organization and having signed an informed inclusion consent
  • definitive diagnosis of high risk myelodysplastic syndrome with excess blasts
  • eligibility to an Azacytidine therapy as first-line treatment
Exclusion Criteria
  • personal history or current other cancer
  • immediate acute myeloid leukemia
  • personal history of demethylation treatment
  • pregnant or breast feeding women
  • life-theatening condition
  • guardianship
  • imprisoned patients

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Patients with High-risk MDS With Excess BlastsMyelogram-
Primary Outcome Measures
NameTimeMethod
Methylation level of the Differentially Methylated Regions (DMR)3 months (after 3 cycles of treatment)
Overall response by IWG 2006 response criteria (complete remission / partial remission / non response)At the treatment response assessment (After 6-12 cycles of treatment up to 52 weeks)
Secondary Outcome Measures
NameTimeMethod
Cytogenetic response by IWG 2006 response criteria (major / minor / no response)At the treatment response assessment (After 6-12 cycles of treatment up to 52 weeks)
Transfusion independence (yes/no)At the treatment response assessment (After 6-12 cycles of treatment up to 52 weeks)
Methylation level of the Differentially Methylated Regions (DMR)At diagnosis
Hematologic improvement by IWG 2006 response criteria (major / minor / no response)At the treatment response assessment (After 6-12 cycles of treatment up to 52 weeks)
General condition improvement (yes/no)At the treatment response assessment (After 6-12 cycles of treatment up to 52 weeks)

Trial Locations

Locations (2)

CHRU de Nancy

🇫🇷

Nancy, France

BROSEUS

🇫🇷

Vandoeuvre les Nancy, France

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