- SUB-TYPE OF MDS:Higher risk MDS, CMML, low blast count AML
- 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)
- NAME OF DRUG: Azacitidine, Pevonedistat
- 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.
- Primary outcome measures:
To determine event-free survival, an event being progression to AML or death.
- Secondary outcome measures:
These include the assessment of complete remission rates, overall survival as well as survival rates at different time points.
- 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.
- 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
- 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.