1. SUB-TYPE OF MDS:Higher risk MDS, CMML, low blast count AML
2. SEVERITY OF MDS: Intermediate, high risk or very high risk MDS as defined by the World Health Organization (WHO) criteria or Revised International Prognostic Scoring System (IPSS-R)
3. NAME OF DRUG: Azacitidine, Pevonedistat
4. Aims and benefits: Pevonedistat prevents the activity of a specific enzyme (Nedd8 activating enzyme) and thus may result in the inhibition of tumour cell growth and survival. This is a phase 3 study to determine if combining Pevonedistat with Azacitidine improves survival when compared with single agent Azacitidine.

1. Primary outcome measures: 
   To determine event-free survival, an event being progression to AML or death.
2. Secondary outcome measures:
   These include the assessment of complete remission rates, overall survival as well as survival rates at different time points.
3. Basic inclusion criteria:
   • Higher risk MDS, CMML, low blast count AML.
   • Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers.
   • - ECOG performance status 0-2.
4. Basic exclusion criteria:
   • Previous treatment for higher risk MDS, CMML or low blast count AML. Treatment with hydroxycarbamide or Lenalidomide is permitted.
   • Eligible for intensive chemotherapy and/or allogeneic stem cell transplant.
   • CNS involvement by AML.
   • Active uncontrolled infection
   • Hepatic impairment
   • Cardiopulmonary disease
5. Trial sites/locations and name of physician in charge of trial:
   • Royal Bournemouth Hospital, Bournemouth
   • Maidstone Hospital, Maidstone, Kent
   • St. Bartholomew’s Hospital, London
   • Singleton Hospital, Swansea

Please read information and always discuss trial information with your own physician.