An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia

David A. Rizzieri, Sarah A Cooley, Olatoyosi Odenike, Lisette Moonan, Kay Hoong Chow, Kimberley Jackson, Xuejing Wang, Leslie Brail, Gautam Borthakur

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Abstract: This open-label, Phase-2 study investigated the safety of LY2090314 (GSK-3 inhibitor) in AML patients. Twenty patients received 40-mg LY2090314 (50-mg ranitidine pretreatment) as follows: Cohort 1 – days 1, 8, and 15 of a 28-d cycle (n = 7); Cohort 2 – days 1, 5, and 9 of a 21-d cycle (n = 6); Cohort 3 – days 1, 5, 9, and 12 of a 21-d cycle (n = 7). Decreased appetite (n = 7) and nausea (n = 4) were the most frequently reported possibly drug-related non-hematologic treatment-emergent adverse events (TEAEs). Hematologic TEAEs included febrile neutropenia (n = 2), thrombocytopenia (n = 1), and anemia (n = 1). Atrial flutter (n = 1), QT interval prolongation (n = 3), and visual disturbances (n = 2) were observed, but were not clinically significant (investigator assessed). Although β-catenin levels indicated an on-target effect, no complete or partial remissions were observed. Pharmacokinetics were consistent with a previous Phase 1 study. These data suggest that single-agent LY2090314 has acceptable safety but limited clinical benefit in AML patients at the dose/frequencies investigated.

Original languageEnglish (US)
Pages (from-to)1800-1806
Number of pages7
JournalLeukemia and Lymphoma
Volume57
Issue number8
DOIs
StatePublished - Aug 2 2016

Keywords

  • AML
  • GSK-3
  • Pharmacotherapy

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