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.
Original language | English (US) |
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Pages (from-to) | 1484-1492 |
Number of pages | 9 |
Journal | Leukemia and Lymphoma |
Volume | 61 |
Issue number | 6 |
DOIs | |
State | Published - May 11 2020 |
Keywords
- AR-42
- Acute myeloid leukemia
- HDAC inhibitor
- REC-2282
- decitabine
- miR-29b
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research