International Randomized Phase III Study of Elacytarabine Versus Investigator Choice in Patients With Relapsed/Refractory Acute Myeloid Leukemia

<jats:sec><jats:title>Purpose</jats:title><jats:p> Most patients with acute myeloid leukemia (AML) eventually experience relapse. Relapsed/refractory AML has a dismal prognosis and currently available treatment options are generally ineffective. The objective of this large, international, randomized clinical trial was to investigate the efficacy of elacytarabine, a novel elaidic acid ester of cytarabine, versus the investigator's choice of one of seven commonly used AML salvage regimens, including high-dose cytarabine, multiagent chemotherapy, hypomethylating agents, hydroxyurea, and supportive care. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> A total of 381 patients with relapsed/refractory AML were treated in North America, Europe, and Australia. Investigators selected a control treatment for individual patients before random assignment. The primary end point was overall survival (OS). </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> There were no significant differences in OS (3.5 v 3.3 months), response rate (23% v 21%), or relapse-free survival (5.1 v 3.7 months) between the elacytarabine and control arms, respectively. There was no significant difference in OS among any of the investigator's choice regimens. Prolonged survival was only achieved in a few patients in both study arms whose disease responded and who underwent allogeneic stem-cell transplantation. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Neither elacytarabine nor any of the seven alternative treatment regimens provided clinically meaningful benefit to these patients. OS in both study arms and for all treatments was extremely poor. Novel agents, novel clinical trial designs, and novel strategies of drug development are all desperately needed for this patient population. </jats:p></jats:sec>