Phase I study of AR-42 and decitabine in acute myeloid leukemia

Abstract

This phase I trial sought to determine a biologically safe and effective dose of AR-42, a novel histone deacetylase inhibitor, which would lead to a doubling of miR-29b prior to decitabine administration. Thirteen patients with previously untreated or relapsed/refractory AML were treated at 3 dose levels (DL): AR-42 20 mg qd on d1,3,5 in DL1, 40 mg qd on d1,3,5 in DL2 and 40 mg qd on d1,3,4,5 in DL3. Patients received decitabine 20 mg/m² on d6–15 of each induction cycle and 20 mg/m² on d6–10 of each maintenance cycle. One DLT of polymicrobial sepsis and multi-organ failure occurred at DL3. Two patients achieved a CRi and one patient achieved a CR for an ORR of 23.1%. The higher risk features of this patient population and the dosing schedule of AR-42 may have led to the observed clinical response and failure to meet the biologic endpoint.

Keywords:

• Acute myeloid leukemia
• HDAC inhibitor
• AR-42
• REC-2282
• decitabine
• miR-29b

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

AR-42 was provided by Arno Therapeutics, Inc. This project was supported by The Ohio State University Comprehensive Cancer Center and Pharmacoanalytical Shared Resource; the Division of Cancer Prevention, National Cancer Institute grants [P30CA016058, K12CA133250] to CCC, [R01CA158350] to RG and GM and [R01CA201382] to MAP; an Eli Lilly Fellowship in Pharmaceutics to SGL; Pelotonia Award to ARW.