Characterization of the Mechanisms of Resistance to Azacitidine

Recruiting

• Conditions: Myelodysplastic Syndromes or Acute Myeloid Leukemia with Multilineage Dysplasia

• Registration Number: NCT01210274
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

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 Description

Not available

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-27
• Study First Submitted QC: 2010-09-27
• Study First Posted: 2010-09-28
• Primary Completion: 2014-09
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-19
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
hematological response	at 6 months	Hematological response evaluated by the International Working Group (IWG) response of Cheson

Secondary Outcome Measures

Name	Time	Method
Overall survival	at the death	Overall survival (OS) defined as the time from start of treatment

Trial Locations

Locations (4)

CH d'Antibes; 🇫🇷 Antibes, France

CHU de Nice - Hôpital de l'Archet; 🇫🇷 Nice, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CH Princesse Grace; 🇲🇨 Monaco, Monaco