The development of new treatments for older patients with acute myeloid leukaemia (AML) is an active area, but has met with limited success. Sapacitabine is a novel orally administered nucleoside analogue that has shown encouraging activity in unrandomised early-stage trials. We randomised 143 untreated patients with AML or with high-risk myelodysplastic syndrome (>10% marrow blasts) between sapacitibine and low-dose ara-C (LDAC) in our ‘Pick a Winner’ trial design. At the planned interim analysis there was no difference between LDAC and sapacitibine in terms of remission rate (CR/CRi, 27% vs 16% hazard ratio (HR) 1.98(0.90–4.39) P=0.09), relapse-free survival (10% vs 14% at 2 years, HR 0.73(0.33–1.61) P=0.4) or overall survival (OS; 12% vs 11% at 2 years, HR 1.24(0.86–1.78) P=0.2). Sapacitibine was well tolerated, apart from more grade 3/4 diarrhoea. On the basis of these findings sapacitibine did not show sufficient evidence of benefit over LDAC for the trial to be continued.
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We are grateful to Cyclacel Ltd for the provision of Sapacitabine for the duration of the study, and to the Haematology Clinical Trials Unit, Cardiff University, for supervising the trial. The following investigators contributed patients to the trial: Aberdeen Royal Infirmary: Dr C Duncan; Addenbrooke's Hospital: Dr C Crawley, Dr J Craig; Airedale General Hospital: Dr A C Cuthbert, Dr C Patalappa; Belfast City Hospital: Dr M F McMullin, Dr R J G Cuthbert; Blackpool Victoria Hospital: Dr P A Cahalin, Dr P R Kelsey; Bradford Royal Infirmary: Dr N Sood, Dr S Ackroyd; Castle Hill Hospital (Hull): Dr S Ali; Cheltenham General Hospital: Dr A Rye; Churchill Hospital: Dr P Vyas; City Hospitals Sunderland: Dr A Nicolle, Dr M J Galloway; Colchester General Hospital: Dr G Campbell, Dr M T Hamblin; Derriford Hospital: Dr T J Nokes; Dorset County Hospital: Dr A Moosa; Gartnavel General Hospital: Dr P McKay; Gloucestershire Royal Hospital: Dr R Frewin; Guy's Hospital: Dr R Carr; Hillingdon Hospital: Dr K Patel, Dr R Kaczmarski; James Paget University Hospital: Dr C Gomez; Kent & Canterbury Hospital: Dr K Saied; Leicester Royal Infirmary: Dr A E Hunter, Dr A M Martin; Medway Maritime Hospital: Dr W Nagi; Musgrove Park Hospital: Dr D Mannari; Norfolk & Norwich University Hospital: Dr M Lawes; North Manchester General Hospital: Dr D Osbourne; North Middlesex Hospital: Dr J Luckit; Northwick Park Hospital: Dr C Kyriakou, Dr N Panoskaltsis; Nottingham University Hospital: Dr E Das-Gupta, Dr J L Byrne, Prof N H Russell; Poole General Hospital: Dr F Jack; Queen Alexandra Hospital (Portsmouth): Dr H Dignum, Dr M Ganczakowski, Dr R Corser; Queen Elizabeth Hospital (Kings Lynn): Dr A J Keidan; Queen's Hospital, Romford: Dr C Hemmaway; Rigshospitalet University Hospital: Dr Lars Kjeldsen, Dr Ove Juul Nielsen; Russells Hall Hospital: Dr S Jenkins; Salford Royal Hospital: Dr S Ravenscroft; Salisbury District Hospital: Dr E Grand, Dr T Everington; Sandwell Hospital: Dr F Wandroo; Singleton Hospital: Dr H Sati, Dr S Al-Ismail; Southampton General Hospital: Dr S Narayanan; St Bartholomew's Hospital: Dr H Oakervee, Dr J Cavenagh; St Helens & Knowsley (Whiston): Dr T Nicholson; St James's University Hospital: Prof D T Bowen; Stoke Mandeville Hospital: Dr A Watson; The James Cook University Hospital: Dr D Plews; The Royal Bournemouth Hospital: Dr J Chacko; The Royal Liverpool Hospital: Dr R Salim; The Royal Oldham Hospital: Dr Allameddine Allameddine, Dr D Osbourne; University College Hospital London: Dr A Khwaja, Dr K G Patterson; University Hospital Aintree: Dr B Hammer, Dr W Sadik; University Hospital of North Tees: Dr Z Maung; University Hospital Of Wales: Dr S Knapper; Victoria Hospital: Dr P Williamson; Western General Hospital: Dr P R E Johnson; Wycombe General Hospital: Dr R Aitchison; York Hospital: Dr L R Bond; Ysbyty Gwynedd: Dr M Hamilton.
AKB has acted on a data monitoring committee for Cyclacel Ltd. The remaining authors declare no conflict of interest.
Supplementary Information accompanies this paper on the Leukemia website
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