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
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
- Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go
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
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
After 4 courses treatment
Lionel Adès, MD
Groupe Francophone des Myélodysplasies
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)