Phase 1 dose escalation trial of volasertib in combination with decitabine in patients with acute myeloid leukemia

Jorge Cortes, Nikolai Podoltsev, Hagop Kantarjian, Gautam Borthakur, Amer M. Zeidan, Maximilian Stahl, Tillmann Taube, Nora Fagan, Sushmita Rajeswari, Geoffrey L. Uy

Research output: Contribution to journalArticle

Abstract

Polo-like kinase 1 (PLK1) regulates mitotic checkpoints and cell division. PLK1 overexpression is reported in numerous cancers, including acute myeloid leukemia (AML), and is associated with poor prognosis. Volasertib is a selective, potent cell-cycle kinase inhibitor that targets PLK to induce mitotic arrest and apoptosis. This phase 1 trial investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of volasertib in combination with decitabine in AML patients aged ≥ 65 years. Thirteen patients were treated with escalating volasertib doses (3 + 3 design; 300 mg, 350 mg, and 400 mg) plus standard-dose decitabine. Dose-limiting toxicity was reported in one patient in cycle 1; the MTD of volasertib in combination with decitabine was determined as 400 mg. The most common treatment-emergent adverse events were febrile neutropenia, pneumonia, and decreased appetite. Objective response rate was 23%. The combination was well tolerated, and the adverse event profile was in line with previous findings.

Original languageEnglish (US)
JournalInternational Journal of Hematology
DOIs
StateAccepted/In press - 2020
Externally publishedYes

Keywords

  • AML
  • Decitabine
  • Phase 1
  • PLK1
  • Volasertib

ASJC Scopus subject areas

  • Hematology

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