Characterization of the Mechanisms of Resistance to Azacitidine
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Purpose
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).
| Condition |
|---|
|
Myelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage Dysplasia |
| Study Type: | Observational |
| Study Design: | Observational Model: Case-Only Time Perspective: Prospective |
| Official Title: | Characterization of the Mechanisms of Action of Resistance to Azacitidine in High-risk Myelodysplastic Syndromes and Acute Myeloid Leukemia With Multilineage Dysplasia |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
Patients with myelodysplastic syndromes or acute myeloid leukemia with multilineage dysplasia treated with Azacitidine
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
Contacts and Locations| France | |
| CHU de Nice - Hôpital de l'Archet | Recruiting |
| Nice, France, 06200 | |
| Contact: Thomas Cluzeau, PH cluzeau.thomas@gmail.com | |
| Principal Investigator: Jill Pa Cassuto, PU-PH | |
More Information
No publications provided by Centre Hospitalier Universitaire de Nice
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Centre Hospitalier Universitaire de Nice |
| ClinicalTrials.gov Identifier: | NCT01210274 History of Changes |
| Other Study ID Numbers: | 10-PP-10 |
| Study First Received: | September 27, 2010 |
| Last Updated: | August 6, 2012 |
| Health Authority: | France: French Data Protection Authority |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases |
Precancerous Conditions Azacitidine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013