Characterization of the Mechanisms of Resistance to Azacitidine

Sponsor

Centre Hospitalier Universitaire de Nice (Other)

Overall Status

Unknown status

CT.gov ID

NCT01210274

Collaborator

(none)

Enrollment

Locations

Duration (Months)

22.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes or Acute Myeloid Leukemia With Multilineage Dysplasia

Study Design

Study Type:

Observational

Anticipated Enrollment :

90 participants

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

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Sep 1, 2014

Anticipated Study Completion Date :

Sep 1, 2018

Outcome Measures

Primary Outcome Measures

hematological response [at 3 months]
Hematological response evaluated by the International Working Group (IWG) response of Cheson
hematological response [at 6 months]
Hematological response evaluated by the International Working Group (IWG) response of Cheson

Secondary Outcome Measures

Overall survival [Day 1 of treatment]
Overall survival (OS) defined as the time from start of treatment
Overall survival [at the death]
Overall survival (OS) defined as the time from start of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	CH d'Antibes	Antibes	France
2	CHU de Nice - Hôpital de l'Archet	Nice	France	06200
3	Centre Antoine Lacassagne	Nice	France
4	CH Princesse Grace	Monaco	Monaco

Sponsors and Collaborators

Centre Hospitalier Universitaire de Nice

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Centre Hospitalier Universitaire de Nice

ClinicalTrials.gov Identifier:

NCT01210274

Other Study ID Numbers:

10-PP-10

First Posted:

Sep 28, 2010

Last Update Posted:

Aug 23, 2017

Last Verified:

Aug 1, 2017

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Study Results

No Results Posted as of Aug 23, 2017