Intensified Azacitidine in High Risk Myelodysplastic Syndrome (MDS)
A phase I/II study of the efficacy and safety of an intensified schedule of Azacitidine (Vidaza®) in intermediate-2 and high risk MDS patients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of the Efficacy and Safety of an Intensified Schedule of Azacitidine (Vidaza®) in Intermediate-2 and High Risk MDS Patients|
- Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks. [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]After 4 courses treatment
- Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE) [ Time Frame: 1-24 months ] [ Designated as safety issue: Yes ]After each course of treatment until end of treatment.
- Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration. [ Time Frame: 2-4 months ] [ Designated as safety issue: No ]After 4 and 8 courses of treatment.
- Overall survival and progression (IPSS/AML) free survival. [ Time Frame: 2 months and further ] [ Designated as safety issue: No ]After 4 course of treatment.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
|Experimental: Azacitidine intensified dose||
Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles.
Other Name: Vidaza
The study is an open-label, multicenter phase I/II study.
Treatment Regimen, Dosage and Duration:
Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles (azacitidine-14, cycles 1-4).
- Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days administered every 21 days (azacitidine-21, cycles 5 to 8) followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (azacitidine-28, cycles 9 and beyond), to be continued until progression/relapse or toxicity arises).
- Patients not obtaining CR or PR after the initial 4 cycles of azacitidine-14 will continue to receive azacitidine 75mg/m2/d for 5 days every 14 days for 4 additional cycles (cycles 5 to 8). If they achieve CR, PR or HI after 8 cycles, they will then be treated with azacitidine 75mg/m2/d for 5 days every 21 days (azacitidine-21, cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (azacitidine-28, cycles 13 and beyond) until progression/relapse or toxicity arises.
- Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go "off-study".
Number of patients to be included:
The trial will enroll at least 27 patients (phase I of the trial) and a maximum of 81 patients (phase II of the trial). A safety analysis will be performed by an independent DSMB after inclusion of 9, 18 and 27 patients. This safety analysis will focus particularly on the clinical consequences of cytopenias. Moreover, a teleconference will be organized twice monthly between the PI and investigators to share safety observations and take appropriate actions if needed. CRFs will be collected every cycle focusing particularly on the safety of this dose intensified study. All AE and SAE will be reported to the DSMB upon reception.
-Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks.
- Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE)
- Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration
- Overall survival and progression (IPSS/AML) free survival.
Sample Size and Duration of Trial:
The first stage of the trial will include 27 patients. The trial will be terminated if 9 or fewer responses are observed. Otherwise, additional patients will be recruited in the second stage until a total sample size of 81 patients is reached.
Duration of inclusion: 24 months for 81 patients Duration of follow-up: 24 months
Please refer to this study by its ClinicalTrials.gov identifier: NCT01305460
|Service d'Hématologie Clinique|
|CHU Albert Michallon, Grenoble, France, 38043|
|Amiens, France, 80054|
|Centre Hospitalier de La Cote Basque|
|Bayonne, France, 64100|
|Bobigny, France, 93009|
|CHU de Haut-Lévèque|
|Bordeaux Pessac, France, 33604|
|Centre henri Mondor|
|Creteil, France, 94010|
|Centre Hospitalier du Mans|
|Le Mans cedex, France, 72037|
|Lille, France, 59037|
|Hôpital Paoli Calmettes|
|Marseille, France, 13273|
|Centre Hospitalier de Meaux|
|Meaux, France, 77100|
|Nancy, France, 54511|
|CHU de nantes|
|Nantes, France, 44093|
|Hôpital l'Archet de Nice|
|Nice, France, 06202|
|Hôpital Saint Louis|
|Paris, France, 75010|
|Paris, France, 75004|
|Hopital Saint Louis - AP-HP, Hematology Dpt|
|Paris, France, 75475|
|CHU de Poitiers|
|Poitiers, France, 86021|
|CHRU Annecy Hospital|
|Pringy, France, 74374|
|Rennes, France, 35033|
|Hopital Purpan Service d'Hématologie Clinique|
|Toulouse, France, 31059|
|CH de Valence|
|Valence, France, 26953|
|Study Chair:||Lionel Adès, MD||Groupe Francophone des Myélodysplasies|
|Principal Investigator:||Simone Boehrer, MD||Groupe Francophone des Myélodysplasies|