Clinical trial · Observational
Characterization of the Mechanisms of Resistance to Azacitidine
Characterization of the Mechanisms of Action of Resistance to Azacitidine in High-risk Myelodysplastic Syndromes and Acute Myeloid Leukemia With Multilineage Dysplasia
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Myelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage Dysplasia | Myelodysplastic Syndrome | ALIAS | 0.90 |
Interventions
Interventions (0)
Data not yet available
Design
Arms and outcomes
Arms (0)
[]Primary outcomes (2)
- measure
- hematological response
- timeFrame
- at 3 months
- description
- Hematological response evaluated by the International Working Group (IWG) response of Cheson
- measure
- hematological response
- timeFrame
- at 6 months
- description
- Hematological response evaluated by the International Working Group (IWG) response of Cheson
Secondary outcomes (2)
- measure
- Overall survival
- timeFrame
- Day 1 of treatment
- description
- Overall survival (OS) defined as the time from start of treatment
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- DERIVEDCluzeau 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