Abstract
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 90 mg/m2 on 5 consecutive days in each 28-day cycle (5-day regimen). Subsequently, another cohort was treated for 10 days with 60 mg/m2 (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 90 mg/m2/d, respectively [5-day regimen] and 53 patients who were assigned to 60 mg/m2/d [10-day regimen]). The 90 mg/m2 dose showed no benefit in clinical outcomes in comparison with 60 mg/m2 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%; P =.1061; CR, 18.9% vs 8%; P =.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. Cancer 2018;124:325-34.
Original language | English (US) |
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Pages (from-to) | 325-334 |
Number of pages | 10 |
Journal | Cancer |
Volume | 124 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2018 |
Keywords
- SGI-110
- acute myeloid leukemia (AML)
- guadecitabine
- refractory
- relapsed
ASJC Scopus subject areas
- Oncology
- Cancer Research