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Original Articles: Clinical

A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas

Douglas W. SborovDivision of Hematology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA;

Alessandro CanellaComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA;

Erinn M. HadeCenter for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA;

Xiaokui MoCenter for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA;

Soun KhounthamComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA;

Jiang WangComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA;

Wenjun NiDivision of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA;

Ming PoiComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; ;Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA;

Christopher CossComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; ;Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA;

Zhongfa LiuDivision of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA;

Mitch A. PhelpsComprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; ;Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA;

Amir MortazaviDivision of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Leslie AndritsosDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Robert A. BaiocchiDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Beth A. ChristianDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Don M. BensonDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Joseph FlynnDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Pierluigi PorcuDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

John C. ByrdDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA;

Flavia PichiorriComprehensive Cancer Center, City of Hope, Duarte, CA, USA

Craig C. HofmeisterDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; Correspondence[email protected]

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Abstract

Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40 mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively. Treatment was associated with reduction of serum CD44, a transmembrane glycoprotein associated with steroid and immunomodulatory drug resistance in MM. Our findings indicate that AR-42 is safe and that further investigation of AR-42 in combination regimens for the treatment of patients with lymphoma and MM is warranted.

Trial registration: http://clinicaltrials.gov/ct2/show/NCT01129193

Keywords:

Funding

This work was supported by the National Cancer Institute [U01CA076576, T32CA165998, R21CA156222].

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/10.1080/10428194.2017.1298751.

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A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas

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A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas

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