Phase 1 dose-escalation study of oral abexinostat for the treatment of patients with relapsed/refractory higher-risk myelodysplastic syndromes, acute myeloid leukemia, or acute lymphoblastic leukemia

Abstract

Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120 mg) twice daily (bid) on Days 1–14 of 21-day cycles. The most common treatment-related grade ≥3 adverse events were thrombocytopenia (29%) and neutropenia (24%), none of which led to discontinuation. Maximum-tolerated dose was not reached. Of 12 evaluable patients, best response was stable disease in 1 patient. This study was closed due to limited clinical benefit. Future development of oral abexinostat 100 mg bid in patients with MDS, AML, or ALL should focus on combination regimens.

ISRCTN registry: 99680465

Keywords:

• Abexinostat
• HDAC inhibitors
• myelodysplastic syndromes
• acute myeloid leukemia
• acute lymphoid leukemia

Acknowledgements

We thank the patients who participated in the study, their supporters, and the investigators and clinical research staff from the study centers. This study was sponsored by Pharmacyclics LLC, an AbbVie Company. This manuscript was developed with editorial support from Stacey Rose, PhD, and funded by Pharmacyclics LLC, an AbbVie Company.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1263843.