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

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 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.

• Authors: Yasmin Abaza, Hagop Kantarjian, Yasmin Alwash, Gautam Borthakur, Richard Champlin, Tapan Kadia, Guillermo Garcia-Manero, Naval Daver, Farhad Ravandi, Srdan Verstovsek, Jan Burger, Zeev Estrov, Maro Ohanian, Miranda Lim, Naveen Pemmaraju, Elias Jabbour, Jorge Cortes
• Journal: American journal of hematology (Am J Hematol) Vol. 95 Issue 11 Pg. 1288-1295 (11 2020) ISSN: 1096-8652 [Electronic] United States
• PMID: 32681739 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Decitabine
• Dasatinib

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Blast Crisis (blood, drug therapy, mortality)
• Dasatinib (administration & dosage, adverse effects)
• Decitabine (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, drug therapy, mortality)
• Leukemia, Myeloid, Acute (blood, drug therapy, mortality)
• Male
• Middle Aged
• Survival Rate