1. 1. SUB-TYPE OF MDS: MDS with 10% or more bone marrow blasts and also acute myeloid leukaemia
   2. SEVERITY OF MDS: Intermediate –2 or High Risk
   3. NAME OF DRUG: AC220 (Quizartinib), Ganetespib, Tosedostat, Selinexor, Lenalidomide and other novel therapies that will become available throughout the course of the study. These are all target treatments that block various pathways in the proliferation or growth of leukaemia cells.

1. Aims and benefits: This study is designed primarily for older patients with AML and high risk MDS who are not considered suitable for conventional/intensive chemotherapy.
   • It compares the effect of low-dose Cytarabine (standard treatment) versus low-dose Cytarabine in combination with a novel drug on overall survival, complete remission and duration of response.
   • It investigates drug toxicity and supportive care requirements and assesses quality of life.
   • Specific questions include the relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission and the relevance of molecular characteristics and other biomarkers to response to treatment.
   • Storage of diagnostic tissue for future research in the AML Cell Bank.
2. Basic inclusion criteria:
   • Acute myeloid leukaemia (excluding acute promyelocytic leukaemia) or high risk Myelodysplastic Syndrome (>10% bone marrow blasts)
   • Age over 60 years
   • Adequate cardiac function
3. Basic exclusion criteria:
   • Age less than 60
   • Patients who previously received demethylation treatment (eg. Azacitidine) for high risk MDS (>10% blasts)
   • Previous chemotherapy for acute myeloid leukaemia
   • Serum creatinine ≥175μmol/L
   • History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 6 months
   • Concurrent active malignancy excluding basal cell carcinoma
   • Pregnant or lactating
   • Known infection with human immunodeficiency virus (HIV)
4. Trial sites/locations and name of physician in charge of trial: 
   • Northwick Park Hospital
   • University Hospital Aintree
   • Salisbury District Hospital
   • St Helens & Knowsley (Whiston)
   • The Royal Oldham Hospital
   • Western General Hospital
   • Arrowe Park Hospital
   • Birmingham Heartlands Hospital
   • University Hospital of Wales
   • Queen Alexandra Hospital (Portsmouth)
   • Derriford Hospital (Plymouth)
   • Basingstoke and North Hampshire Hospital
   • Queens Hospital (Romford)
   • The Royal Bournemouth Hospital
   • University Hospital of North Tees
   • The Royal Liverpool University Hospital
   • Countess of Chester Hospital
   • Stoke Mandeville Hospital
   • Wycombe Hospital
   • Aberdeen Royal Infirmary
   • Bradford Royal Infirmary
   • Bristol Haematology & Oncology Centre
   • Blackpool Victoria Hospital
   • The Christie Peterborough City Hospital
   • Colchester General Hospital
   • New Cross Hospital
   • Nottingham University Hospital
   • Russells Hall Hospital
   • University College Hospital London
   • St Richard's Hospital
   • Airedale General Hospital
   • The James Cook University Hospital
   • Castle Hill Hospital
   • Royal Cornwall Hospital
   • Poole General Hospital
   • St. James's University Hospital
   • Sandwell Hospital
   • Southampton General Hospital
   • Singleton Hospital
   • Leicester Royal Infirmary
   • Medway Maritime Hospital
   • NHS Fife (Victoria Hospital, Kirkaldy)
   • Pinderfields Hospital
   • Belfast City Hospital
   • Barnet Hospital
   • Kettering General Hospital
   • Lincoln County Hospital
   • Eastbourne District General Hospital
   • Conquest Hospital
   • NHS Lanarkshire (Monklands Hospital)
   • Beatson West of Scotland Cancer Centre
   • NHS Lanarkshire (Hairmyres Hospital)
   • NHS Lanarkshire (Wishaw General)
   • Royal Berkshire Hospital
   • Stafford Hospital
   • Forth Valley Royal Hospital
   • Royal Devon & Exeter Hospital
   • Northampton General Hospital
   • Great Western Hospital
   • Hereford County Hospital
   • NHS Ayrshire & Arran (Crosshouse Hospital)
   • NHS Ayrshire & Arran (Ayr Hospital)
   • Ysbyty Glan Clywd (Rhyl)
   • Ysbyty Gwynedd (Bangor)
   • Gloucestershire Royal Infirmary
   • Cheltenham General Hospital
   • Pilgrim Hospital
   • Grantham District Hospital
   • Southport and Formby District General Hospital
   • Yeovil District Hospital
   • Sunderland Royal Hospital
   • New Victoria Hospital
   • Queen Elizabeth Hospital Kings Lynn
   • Ipswich Hospital
   • Huddersfield Royal Infirmary
   • Basildon University Hospital
   • Addenbrooke's Hospital

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