Format

Send to

Choose Destination
Leuk Lymphoma. 2017 Aug;58(8):1880-1886. doi: 10.1080/10428194.2016.1263843. Epub 2016 Dec 2.

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.

Author information

1
a Department of Hematology , Institut Paoli Calmettes, SIRIC-Marseille , Marseille , France.
2
b Aix-Marseille University , Marseille , France.
3
c Internal Medicine Department, Section of Hematology , Yale Cancer Center at Yale University , New Haven , CT , USA.
4
d Department of Medical Pharmacology , CIC 1436, Université Toulouse Hospital, Inserm , Toulouse , France.
5
e Department of Oncology Research and Development , Institut de Recherches Internationales Servier , Suresnes , France.
6
f Biometrics, Pharmacyclics , LLC, an AbbVie Company , Sunnyvale , CA , USA.
7
g Department of Clinical Science, Pharmacyclics , LLC, an AbbVie Company , Sunnyvale , CA , USA.
8
h Service d'Hématologie , Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole , Toulouse , France.
9
i Cancer Research Center of Toulouse, UMR1037-INSERM, ERL5294-CNRS , Toulouse , France.

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; acute lymphoid leukemia; acute myeloid leukemia; myelodysplastic syndromes

PMID:
27911138
DOI:
10.1080/10428194.2016.1263843
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center