%0 Journal Article
%T Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS)
%A Azra Raza
%A Naomi Galili
%A Deborah Mulford
%A Scott E. Smith
%A Gail Brown
%A David P. Steensma
%A Roger M. Lyons
%A Ralph Boccia
%A Mikkael A. Sekeres
%A Garcia-Manero Guillermo
%A Ruben A. Mesa
%J Journal of Hematology & Oncology
%D 2012
%I BioMed Central
%R 10.1186/1756-8722-5-18
%X Ezatiostat was administered to 19 patients with non-deletion(5q) myelodysplastic syndrome (MDS) at one of two doses (2000£¿mg or 2500£¿mg/day) in combination with 10£¿mg of lenalidomide on days 1¨C21 of a 28-day cycle. No unexpected toxicities occurred and the incidence and severity of adverse events (AEs) were consistent with that expected for each drug alone. The most common non-hematologic AEs related to ezatiostat in combination with lenalidomide were mostly grade 1 and 2 fatigue, anorexia, nausea, diarrhea, and vomiting; hematologic AEs due to lenalidomide were thrombocytopenia, neutropenia, and anemia. One of 4 evaluable patients (25%) in the 2500/10£¿mg dose group experienced an erythroid hematologic improvement (HI-E) response by 2006 MDS International Working Group (IWG) criteria. Four of 10 evaluable patients (40%) in the 2000£¿mg/10£¿mg dose group experienced an HI-E response. Three of 7 (43%) red blood cell (RBC) transfusion-dependent patients became RBC transfusion independent, including one patient for whom prior lenalidomide monotherapy was ineffective. Three of 5 (60%) thrombocytopenic patients had an HI-platelet (HI-P) response. Bilineage HI-E and HI-P responses occurred in 3 of 5 (60%), 1 of 3 with HI-E and HI-N (33%), and 1 of 3 with HI-N and HI-P (33%). One of 3 patients (33%) with pancytopenia experienced a complete trilineage response. All multilineage responses were observed in the 2000/10£¿mg doses recommended for future studies.The tolerability and activity profile of ezatiostat co-administered with lenalidomide supports the further development of ezatiostat in combination with lenalidomide in MDS and also encourages studies of this combination in other hematologic malignancies where lenalidomide is active.Clinicaltrials.gov: NCT01062152
%K MDS
%K Ezatiostat
%K Lenalidomide
%K Phase 1
%K Non-deletion (5q)
%U http://www.jhoonline.org/content/5/1/18/abstract