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

Leuk Res. 2013 Sep;37(9):1100-6. doi: 10.1016/j.leukres.2013.04.025. Epub 2013 Jun 5.

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.

Trial registration: ClinicalTrials.gov NCT01080664.

Keywords: Aurora kinase inhibitor; Hematologic malignancies; MSC1992371A; Phase l.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Hematologic Neoplasms / drug therapy*
  • Hematologic Neoplasms / enzymology
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Remission Induction
  • Tissue Distribution

Substances

  • Protein Kinase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT01080664