Characterization of the Mechanisms of Resistance to Azacitidine
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Myelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage Dysplasia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France, Monaco
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Characterization of the Mechanisms of Action of Resistance to Azacitidine in High-risk Myelodysplastic Syndromes and Acute Myeloid Leukemia With Multilineage Dysplasia
Overview
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).
Primary outcome measures
- hematological response [Time frame: at 3 months]
- hematological response [Time frame: at 6 months]
Secondary outcome measures (2)
- Overall survival [Time frame: Day 1 of treatment]
- Overall survival [Time frame: at the death]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Case-only
Study locations
France · 3 centers
- CH d'Antibes — Antibes
- CHU de Nice - Hôpital de l'Archet — Nice
- Centre Antoine Lacassagne — Nice
Monaco · 1 center
- CH Princesse Grace — Monaco
Publications
- Cluzeau T, Robert G, Mounier N, Karsenti JM, Dufies M, Puissant A, Jacquel A, Renneville A, Preudhomme C, Cassuto JP, Raynaud S, Luciano F, Auberger P. BCL2L10 is a predictive factor for resistance to azacitidine in MDS and AML patients. Oncotarget. 2012 Apr;3(4):490-501. doi: 10.18632/oncotarget.481. PMID 22577154
Identifiers
NCT: NCT01210274 · 10-PP-10