A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia

Research output: Contribution to journalArticle

Authors

  • B Vormoor
  • G J Veal
  • M J Griffin
  • A V Boddy
  • J Irving
  • L Minto
  • M Case
  • U Banerji
  • K E Swales
  • J R Tall
  • A S Moore
  • M Toguchi
  • G Acton
  • K Dyer
  • C Schwab
  • C J Harrison
  • J D Grainger
  • D Lancaster
  • D Hargrave
  • J Vormoor

Colleges, School and Institutes

External organisations

  • Newcastle University
  • Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, U.K.
  • Astex Pharmaceuticals, Cambridge Science Park, Cambridge, UK.
  • Cancer Research UK Centre for Drug Development, London, UK.
  • Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
  • Drug Development Unit, The Royal Marsden Hospital, Institute of Cancer Research, Downs Road, Sutton, Surrey, SM2 5PT, UK, rhoda.molife@icr.ac.uk.
  • Institute of Cancer and Genomic Medicine, University of Birmingham, Birmingham, UK.
  • Great Ormond Street Hospital for Children, London, UK.

Abstract

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.

Details

Original languageEnglish
JournalPediatric Blood & Cancer
Early online date1 Dec 2016
Publication statusE-pub ahead of print - 1 Dec 2016