Dose, Schedule, Safety, and Efficacy of Guadecitabine in Relapsed or Refractory Acute Myeloid Leukemia

BACKGROUND: Outcomes for patients with relapsed or refractory acute myeloid leukemia (AML) are poor. Guadecitabine, a next-generation hypomethylating agent, could be useful in treating such patients. METHODS: In this multicenter, open-label, phase 2 dose-expansion study, AML patients from 10 North American medical centers were first randomized (1:1) to receive subcutaneous guadecitabine at 60 or 90mg/m(2) on 5 consecutive days in each 28-day cycle (5-day regimen). Subsequently, another cohort was treated for 10 days with 60mg/m(2) (10-day regimen). RESULTS: Between June 15, 2012, and August 19, 2013, 108 patients with previously treated AML consented to enroll in the study, and 103 of these patients were treated; 5 patients did not receive the study treatment. A total of 103 patients were included in the safety and efficacy analyses (24 and 26 patients who were randomly assigned to 60 and 90mg/m(2)/d, respectively [5-day regimen] and 53 patients who were assigned to 60mg/m(2)/d [10-day regimen]). The 90mg/m(2) dose showed no benefit in clinical outcomes in comparison with 60mg/m(2) in the randomized cohort. Composite complete response (CRc) and complete response (CR) rates were higher with the 10-day regimen versus the 5-day regimen (CRc, 30.2% vs 16.0%; P5.1061; CR, 18.9% vs 8%; P5.15). Adverse events (grade > 3) were mainly hematologic, with a higher incidence on the 10-day regimen. Early all-cause mortality was low and similar between regimens. Twenty patients (8 on the 5-day regimen and 12 on the 10-day regimen) were bridged to hematopoietic cell transplantation. CONCLUSIONS: Guadecitabine has promising clinical activity and an acceptable safety profile and thus warrants further development in this population. (C) 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.