TY - JOUR
T1 - An open-label phase 2 study of glycogen synthase kinase-3 inhibitor LY2090314 in patients with acute leukemia
AU - Rizzieri, David A.
AU - Cooley, Sarah A
AU - Odenike, Olatoyosi
AU - Moonan, Lisette
AU - Chow, Kay Hoong
AU - Jackson, Kimberley
AU - Wang, Xuejing
AU - Brail, Leslie
AU - Borthakur, Gautam
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2016/8/2
Y1 - 2016/8/2
N2 - 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.
AB - 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.
KW - AML
KW - GSK-3
KW - Pharmacotherapy
UR - http://www.scopus.com/inward/record.url?scp=84953314388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84953314388&partnerID=8YFLogxK
U2 - 10.3109/10428194.2015.1122781
DO - 10.3109/10428194.2015.1122781
M3 - Article
C2 - 26735141
AN - SCOPUS:84953314388
SN - 1042-8194
VL - 57
SP - 1800
EP - 1806
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -