An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes

Stuart L Goldberg; Pierre Fenaux; Michael D Craig; Emmanuel Gyan; John Lister; Jeannine Kassis; Arnaud Pigneux; Gary J Schiller; JungAh Jung; E Jane Leonard; Howard Fingert; Peter Westervelt

doi:10.1016/j.lrr.2014.06.003

An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes

Leuk Res Rep. 2014 Jul 5;3(2):58-61. doi: 10.1016/j.lrr.2014.06.003. eCollection 2014.

Authors

Affiliations

¹ John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
² Service d׳hématologie Clinique, Hôpital Avicenne (AP-HP)/Université, Paris 13, Bobigny, France.
³ Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV, USA.
⁴ Service d׳hématologie et Thérapie Cellulaire, CNRS UMR 7292, CHRU de Tours, France.
⁵ Division of Hematology and Cellular Therapy, Western Pennsylvania Cancer Institute, Pittsburgh, PA, USA.
⁶ Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
⁷ Service d׳hématologie CHU Bordeaux, Pessac, France.
⁸ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁹ Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
¹⁰ Division of Oncology, Washington University Medical School, St. Louis, MO, USA.

Abstract

Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.

Keywords: Acute myeloid leukemia (AML); Alisertib; Aurora A kinase inhibitor; Myelodysplastic syndrome (MDS); Safety.