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Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia
Author(s) -
Abaza Yasmin,
Kantarjian Hagop,
Alwash Yasmin,
Borthakur Gautam,
Champlin Richard,
Kadia Tapan,
GarciaManero Guillermo,
Daver Naval,
Ravandi Farhad,
Verstovsek Srdan,
Burger Jan,
Estrov Zeev,
Ohanian Maro,
Lim Miranda,
Pemmaraju Naveen,
Jabbour Elias,
Cortes Jorge
Publication year - 2020
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.25939
Subject(s) - decitabine , dasatinib , medicine , regimen , myeloid leukemia , adverse effect , phases of clinical research , oncology , toxicity , gastroenterology , imatinib , biochemistry , gene expression , dna methylation , gene , chemistry
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/m 2 or 20 mg/m 2 daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m 2 or 20 mg/m 2 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 who achieved a hematologic response compared to non‐responders (not reached vs 4.65 months; P < .001). Decitabine plus dasatinib is a safe and active regimen in advanced CML. Further studies using this combination are warranted.