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

Graux, Carlos;Sonet, Anne;Maertens, Johan;Duyster, Justus;Ottmann, Oliver G;et.al.
(2013) Leukemia Research — Vol. 37, n° 9, p. 1100-1106 (2013)

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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 28 mg/m(2)/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.
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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 (Original work published 2013)