A phase I study of midostaurin and azacitidine in relapsed and elderly AML patients

Clinical Lymphoma, Myeloma & Leukemia
Brenda W CooperHillard M Lazarus

Abstract

Midostaurin is a novel, orally available Fms-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitor that induces cell cycle arrest and apoptosis of leukemic cells expressing mutant and wild type FLT3 receptors, and has shown potential synergism with cytotoxic chemotherapy. We conducted a phase I study of azacitidine (intravenous 75 mg/m(2) daily for 7 days) with escalating doses of oral midostaurin (25 mg twice per day [b.i.d.], 50 mg b.i.d., and 75 mg b.i.d.) on days 8 to 21 of a 28-day cycle in untreated acute myeloid leukemia (AML) in older patients and/or relapsed AML. Patients were eligible regardless of FLT3 mutation status. Trough blood samples for pharmacokinetics were obtained on days 8, 15, and 21 before midostaurin dosing. Seventeen patients with a median age of 73 (range, 57-83) years were enrolled; 5 patients had previous conventional treatment and none of the patients had FLT3 mutations. Dose-limiting toxicities were not observed. Hospitalizations, primarily for infections, occurred in one-third of treatment cycles. Fourteen patients were evaluable for response: 3 attained complete remission and 2 had hematologic improvement. Median (range) survival from enrollment was 6 (1 to ≥ 19) months. Three patients died wi...Continue Reading

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Citations

Jan 24, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·T M KadiaH Kantarjian
Jul 2, 2016·Blood Cancer Journal·I De Kouchkovsky, M Abdul-Hay
Jun 3, 2017·Leukemia & Lymphoma·Vijaya Raj BhattLori J Maness
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Apr 21, 2020·Expert Review of Hematology·Xavier ThomasMaël Heiblig
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