Clinical Trial: Characterization of the Mechanisms of Resistance to Azacitidine

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

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

Brief Summary:

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).

Detailed Summary:
Sponsor: Centre Hospitalier Universitaire de Nice

Current Primary Outcome:

• hematological response [ Time Frame: at 3 months ]
  Hematological response evaluated by the International Working Group (IWG) response of Cheson
• hematological response [ Time Frame: at 6 months ]
  Hematological response evaluated by the International Working Group (IWG) response of Cheson

Original Primary Outcome:

Current Secondary Outcome:

• Overall survival [ Time Frame: Day 1 of treatment ]
  Overall survival (OS) defined as the time from start of treatment
• Overall survival [ Time Frame: at the death ]
  Overall survival (OS) defined as the time from start of treatment

Original Secondary Outcome:

Information By: Centre Hospitalier Universitaire de Nice

Dates:
Date Received: September 27, 2010
Date Started: September 2010
Date Completion: September 2018
Last Updated: August 2, 2016
Last Verified: May 2016