Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia

American Journal of Hematology
Yasmin AbazaJorge Cortes

Abstract

Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this setting. We conducted a phase I/II study to determine safety and efficacy of the combination of dasatinib and decitabine in patients with advanced CML. Two different dose schedules were investigated with a starting decitabine dose of either 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 140 mg daily. Thirty patients were enrolled, including seven with accelerated-phase CML, 19 with blast-phase CML, and four with Philadelphia-chromosome positive acute myeloid leukemia. No dose-limiting toxicity was observed at the starting dose level with either schedule. Grade ≥3 treatment emergent hematological adverse events were reported in 28 patients. Thirteen patients (48%) achieved a major hematologic response and six (22%) achieved a minor hematologic response, with 44% of these patients achieving a major cytogenetic response and 33% achieving a major molecular response. Median overall survival (OS) was 13.8 months, with significantly higher OS among patients wh...Continue Reading

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Citations

Jan 7, 2021·Cancers·Luca MologniAlfonso Zambon
Mar 20, 2021·Journal of Hematology & Oncology·Jorge Cortes, Fabian Lang
Mar 29, 2021·Blood Reviews·Afaf E G Osman, Michael W Deininger
Jun 17, 2021·Journal of Hematology & Oncology·Kapil SaxenaNicholas J Short

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