Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: A multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial

Uwe Platzbecker, Raymond S M Wong, Amit K. Verma, Camille Abboud, Sergio Araujo, Tzeon Jye Chiou, John Feigert, Su Peng Yeh, Katharina Götze, Norbert Claude Gorin, Peter Greenberg, Suman Kambhampati, Yoo Jin Kim, Je Hwan Lee, Roger Lyons, Marco Ruggeri, Valeria Santini, Gregory Cheng, Jun Ho Jang, Chien Yuan ChenBrendan Johnson, John Bennett, Frank Mannino, Yasser Mostafa Kamel, Nicole Stone, Souria Dougherty, Geoffrey Chan, Aristoteles Giagounidis

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Abstract

Background: Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options. Platelet transfusions provide transient benefit and are limited by alloimmunisation. Eltrombopag, an oral thrombopoietin receptor agonist, increases platelet counts and has preclinical antileukaemic activity. We aimed to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adult patients with advanced myelodysplastic syndrome, secondary acute myeloid leukaemia after myelodysplastic syndrome, or de-novo acute myeloid leukaemia. Methods: We did this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial at 37 centres in ten countries in Europe, east Asia, and the Americas. Patients aged 18 years or older who had relapsed or refractory disease or were ineligible for standard treatments; had platelet counts of less than 30 × 109 platelets per L; had 10-50% bone-marrow blasts; or were platelet transfusion dependent were randomly assigned (2:1), via a telephone-based interactive voice-response system (GlaxoSmithKline Registration and Medication Ordering System) with a permuted-block randomisation schedule (block size of three), to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg to a maximum dose of 300 mg. Randomisation was stratified by presence of poor-prognosis (complex) karyotype (presence of at least three abnormalities, or chromosome 7 abnormalities, vs absence) and bone-marrow blast count (

Original languageEnglish (US)
JournalThe Lancet Haematology
Volume2
Issue number10
DOIs
StatePublished - 2015

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ASJC Scopus subject areas

  • Hematology

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Platzbecker, U., Wong, R. S. M., Verma, A. K., Abboud, C., Araujo, S., Chiou, T. J., Feigert, J., Yeh, S. P., Götze, K., Gorin, N. C., Greenberg, P., Kambhampati, S., Kim, Y. J., Lee, J. H., Lyons, R., Ruggeri, M., Santini, V., Cheng, G., Jang, J. H., ... Giagounidis, A. (2015). Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: A multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial. The Lancet Haematology, 2(10). https://doi.org/10.1016/S2352-3026(15)00149-0