Characterization of the Mechanisms of Resistance to Azacitidine

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Centre Hospitalier Universitaire de Nice
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT01210274
First received: September 27, 2010
Last updated: August 2, 2016
Last verified: May 2016
  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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • hematological response [ Time Frame: at 3 months ] [ Designated as safety issue: Yes ]
    Hematological response evaluated by the International Working Group (IWG) response of Cheson

  • hematological response [ Time Frame: at 6 months ] [ Designated as safety issue: Yes ]
    Hematological response evaluated by the International Working Group (IWG) response of Cheson


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Day 1 of treatment ] [ Designated as safety issue: Yes ]
    Overall survival (OS) defined as the time from start of treatment

  • Overall survival [ Time Frame: at the death ] [ Designated as safety issue: Yes ]
    Overall survival (OS) defined as the time from start of treatment


Biospecimen Retention:   Samples With DNA
bone marrow samples

Estimated Enrollment: 90
Study Start Date: September 2010
Estimated Study Completion Date: September 2018
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with myelodysplastic syndromes or acute myeloid leukemia with multilineage dysplasia treated with Azacitidine
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01210274

Locations
France
CH d'Antibes Recruiting
Antibes, France
Contact: Vanina OLIVERI, Project Manaer       oliveri.v@chu-nice.fr   
Principal Investigator: Daniel RE, PH         
CHU de Nice - Hôpital de l'Archet Recruiting
Nice, France, 06200
Contact: Vanina OLIVERI, Project Manager       oliveri.v@chu-nice.fr   
Principal Investigator: Thomas CLUZEAU, PH         
Centre Antoine Lacassagne Recruiting
Nice, France
Contact: Vanina OLIVERI, Project Manager       oliveri.v@chhu-nice.fr   
Principal Investigator: Antoine THYSS, PU-PH         
Sub-Investigator: Frederic PEYRADE, PH         
Sub-Investigator: Lauris GASTAUD, PH         
Monaco
CH Princesse Grace Recruiting
Monaco, Monaco
Contact: Vanina OLIVERI, Project Manager       oliveri.v@chu-nice.fr   
Principal Investigator: Georges GARNIER, PH         
Sub-Investigator: Philippe HEUDIER, PH         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
  More Information

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 2, 2016
Health Authority: France: French Data Protection Authority

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease
Pathologic Processes
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 22, 2016