Characterization of the Mechanisms of Resistance to Azacitidine

Myelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage Dysplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01210274
• Other study ID #: 10-PP-10
• Status: Recruiting
• Phase: N/A
• First received: September 27, 2010
• Last updated: August 22, 2017
• Start date: September 2010
• Est. completion date: September 2018

Study information

• Verified date: August 2017
• Source: Centre Hospitalier Universitaire de Nice
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: September 2018
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage Dysplasia
• Preleukemia
• Syndrome

Locations

Country	Name	City	State
France	CH d'Antibes	Antibes
France	Centre Antoine Lacassagne	Nice
France	CHU de Nice - Hôpital de l'Archet	Nice
Monaco	CH Princesse Grace	Monaco

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Countries where clinical trial is conducted

France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hematological response	Hematological response evaluated by the International Working Group (IWG) response of Cheson	at 3 months
Primary	hematological response	Hematological response evaluated by the International Working Group (IWG) response of Cheson	at 6 months
Secondary	Overall survival	Overall survival (OS) defined as the time from start of treatment	Day 1 of treatment
Secondary	Overall survival	Overall survival (OS) defined as the time from start of treatment	at the death