A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies

Carlos Graux*, Anne Sonet, Johan Maertens, Justus Duyster, Jochen Greiner, Yves Chalandon, Giovanni Martinelli, Dagmar Hess, Dominik Heim, Francis J. Giles, Kevin R. Kelly, Athos Gianella-Borradori, Blandine Longerey, Ekaterine Asatiani, Narmyn Rejeb, Oliver G. Ottmann

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28mg/m2/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses.

Original languageEnglish (US)
Pages (from-to)1100-1106
Number of pages7
JournalLeukemia Research
Volume37
Issue number9
DOIs
StatePublished - Sep 1 2013

Keywords

  • Aurora kinase inhibitor
  • Hematologic malignancies
  • MSC1992371A
  • Phase l

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Graux, C., Sonet, A., Maertens, J., Duyster, J., Greiner, J., Chalandon, Y., Martinelli, G., Hess, D., Heim, D., Giles, F. J., Kelly, K. R., Gianella-Borradori, A., Longerey, B., Asatiani, E., Rejeb, N., & Ottmann, O. G. (2013). A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies. Leukemia Research, 37(9), 1100-1106. https://doi.org/10.1016/j.leukres.2013.04.025