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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rizzieri, DA; Cooley, S; Odenike, O; Moonan, L; Chow, KH; Jackson, K; Wang, X; Brail, L; Borthakur, G

Published Date

  • August 2016

Published In

Volume / Issue

  • 57 / 8

Start / End Page

  • 1800 - 1806

PubMed ID

  • 26735141

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

International Standard Serial Number (ISSN)

  • 1042-8194

Digital Object Identifier (DOI)

  • 10.3109/10428194.2015.1122781

Language

  • eng