Intensified Azacitidine in High Risk Myelodysplastic Syndrome (MDS)
Condition: Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.

      Primary Endpoint:

      -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.

      Secondary Endpoints:

        -  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
    

Intervention name(s): Azacitidine
Intervention type(s): Drug
Intervention description(s): Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles.
Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days every 21 days followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (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 (cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (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".
Other intervention name(s): Vidaza
Intervention MeSH terms: Azacitidine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment