Characterization of the Mechanisms of Resistance to Azacitidine

August 22, 2017 updated by: Centre Hospitalier Universitaire de Nice

Characterization of the Mechanisms of Action of Resistance to Azacitidine in High-risk Myelodysplastic Syndromes and Acute Myeloid Leukemia With Multilineage Dysplasia

Myelodysplastic syndromes (MDS) are frequent diseases in elderly patients (median age: 71 years). IPSS classification defines low risk (Low and Intermediate 1), and high risk (Intermediate 2 and High) MDS. High-risk MDS (MDS-HR) have a high risk of transformation into acute leukemia with multilineage dysplasia (AML-DML). The success of Azacitidine has been mainly achieved through a rigorous empirical and clinical research, but the molecular mechanisms by which this molecule exerts its effects remain poorly characterized. The primary mode of action of Azacytidine is through DNA demethylation, and integration in to mRNA that favor traduction inhibition. The impact of this molecule on various cell death programs involved in the elimination of leukemic cells : apoptosis and autophagy is currently poorly known.

The research program and clinical studies we proposed focus on two major aspects:

- Main objective: Molecular mechanism of action and resistance to Azacitidine: Role of apoptosis versus autophagy.

- Secondary Objective: Reversion of Azacytidine resistance using different drugs targeting apoptosis and/or autophagy. Our laboratory has identified new molecules to selectively induce different types of cell death (apoptosis or autophagy).

Study Overview

Status

Unknown

Conditions

Study Type

Observational

Enrollment (Anticipated)

90

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
      • Antibes, France
        • Recruiting
        • CH d'Antibes
        • Contact:
        • Principal Investigator:
          • Daniel RE, PH
      • Nice, France
        • Recruiting
        • Centre Antoine Lacassagne
        • Contact:
        • Principal Investigator:
          • Antoine THYSS, PU-PH
        • Sub-Investigator:
          • Frederic PEYRADE, PH
        • Sub-Investigator:
          • Lauris GASTAUD, PH
      • Nice, France, 06200
        • Recruiting
        • CHU de Nice - Hôpital de l'Archet
        • Contact:
        • Principal Investigator:
          • Thomas CLUZEAU, PH
  • Monaco
      • Monaco, Monaco
        • Recruiting
        • CH Princesse Grace
        • Contact:
        • Principal Investigator:
          • Georges GARNIER, PH
        • Sub-Investigator:
          • Philippe HEUDIER, PH

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with myelodysplastic syndromes or acute myeloid leukemia with multilineage dysplasia treated with Azacitidine

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • High Risk or Intermediate 2 MDS (IPSS)
  • AML-MD (WHO classification)
  • Treatment with minimum three to six cycles of Azacitidine
  • Informed consent form signed

Exclusion Criteria:

  • Treatment with others chemotherapies alone or in association

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: Case-Only
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
hematological response
Time Frame: at 3 months
Hematological response evaluated by the International Working Group (IWG) response of Cheson
at 3 months
hematological response
Time Frame: at 6 months
Hematological response evaluated by the International Working Group (IWG) response of Cheson
at 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Day 1 of treatment
Overall survival (OS) defined as the time from start of treatment
Day 1 of treatment
Overall survival
Time Frame: at the death
Overall survival (OS) defined as the time from start of treatment
at the death

Collaborators and Investigators

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

Sponsor

Centre Hospitalier Universitaire de Nice

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2010

Primary Completion (Actual)

September 1, 2014

Study Completion (Anticipated)

September 1, 2018

Study Registration Dates

First Submitted

September 27, 2010

First Submitted That Met QC Criteria

September 27, 2010

First Posted (Estimate)

September 28, 2010

Study Record Updates

Last Update Posted (Actual)

August 23, 2017

Last Update Submitted That Met QC Criteria

August 22, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10-PP-10

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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