title: A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas.
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.
  
  
  BACKGROUND
  http://clinicaltrials.gov/ct2/show/NCT01129193.
authors.affiliation: a Division of Hematology, Department of Internal Medicine , University of Utah , Salt Lake City , UT , USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Sborov
authors.affiliation: b Comprehensive Cancer Center , The Ohio State University , Columbus , OH , USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Canella
authors.affiliation: c Center for Biostatistics, Department of Biomedical Informatics , The Ohio State University , Columbus , OH , USA.
authors.forename: Erinn M
authors.initials: EM
authors.lastname: Hade
authors.affiliation: c Center for Biostatistics, Department of Biomedical Informatics , The Ohio State University , Columbus , OH , USA.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.affiliation: b Comprehensive Cancer Center , The Ohio State University , Columbus , OH , USA.
authors.forename: Soun
authors.initials: S
authors.lastname: Khountham
authors.affiliation: b Comprehensive Cancer Center , The Ohio State University , Columbus , OH , USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: d Division of Pharmaceutics, College of Pharmacy , The Ohio State University , Columbus , OH , USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ni
authors.affiliation: b Comprehensive Cancer Center , The Ohio State University , Columbus , OH , USA.|d Division of Pharmaceutics, College of Pharmacy , The Ohio State University , Columbus , OH , USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Poi
authors.affiliation: b Comprehensive Cancer Center , The Ohio State University , Columbus , OH , USA.|d Division of Pharmaceutics, College of Pharmacy , The Ohio State University , Columbus , OH , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coss
authors.affiliation: d Division of Pharmaceutics, College of Pharmacy , The Ohio State University , Columbus , OH , USA.
authors.forename: Zhongfa
authors.initials: Z
authors.lastname: Liu
authors.affiliation: b Comprehensive Cancer Center , The Ohio State University , Columbus , OH , USA.|d Division of Pharmaceutics, College of Pharmacy , The Ohio State University , Columbus , OH , USA.
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
authors.affiliation: e Division of Medical Oncology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Mortazavi
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Andritsos
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Christian
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Flynn
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: g Comprehensive Cancer Center , City of Hope , Duarte , CA , USA.
authors.forename: Flavia
authors.initials: F
authors.lastname: Pichiorri
authors.affiliation: f Division of Hematology, Department of Internal Medicine , The Ohio State University , Columbus , OH , USA.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Hofmeister
mesh_terms: D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D009101:Multiple Myeloma / Q000188:drug therapy; D010654:Phenylbutyrates / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: C524513:HDAC-42; D056572:Histone Deacetylase Inhibitors; D010654:Phenylbutyrates
keywords: Histone deacetylase inhibitor; lymphoma; multiple myeloma; pharmacokinetics; phase 1