Open Access Open Badges Research

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)

Azra Raza1*, Naomi Galili1, Deborah Mulford2, Scott E Smith3, Gail L Brown4, David P Steensma5, Roger M Lyons6, Ralph Boccia7, Mikkael A Sekeres8, Guillermo Garcia-Manero9 and Ruben A Mesa10

Author Affiliations

1 Columbia University Medical Center, New York, NY, USA

2 University of Rochester, Rochester, NY, USA

3 Cardinal Bernardin Cancer Center, Loyola University Chicago Medical Center, Maywood, IL, USA

4 Telik, Inc., Palo Alto, CA, USA

5 Dana-Farber Cancer Institute, Boston, MA, USA

6 Cancer Care Centers South Texas/US Oncology, San Antonio, TX, USA

7 Center for Cancer & Blood Disorders, Bethesda, MD, USA

8 Hematologic Oncology & Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

9 Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

10 Mayo Clinic, Scottsdale, AZ, USA

For all author emails, please log on.

Journal of Hematology & Oncology 2012, 5:18  doi:10.1186/1756-8722-5-18

Published: 30 April 2012



Ezatiostat, a glutathione S-transferase P1-1 inhibitor, promotes the maturation of hematopoietic progenitors and induces apoptosis in cancer cells.


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 1–21 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.

Trial registration NCT01062152

MDS; Ezatiostat; Lenalidomide; Phase 1; Non-deletion (5q)