No Overall Survival Improvement With Elacytarabine vs Investigator Choice in Patients With Relapsed/Refractory AML


Key Points

  • Elacytarabine was not associated with improvement in overall survival, relapse-free survival, or response rate vs investigator’s choice.
  • Overall survival was poor in both groups, with prolonged survival observed in a few patients with response who went on to allogeneic stem-cell transplantation.

Current treatment options for relapsed/refractory acute myeloid leukemia (AML), which carries a very poor prognosis, are generally ineffective. In a phase III trial (CLAVELA) reported in the Journal of Clinical Oncology, Roboz et al found that elacytarabine, a novel elaidic acid ester of cytarabine, provided no overall survival or relapse-free survival benefit compared with investigator’s choice in this setting.

Elacytarabine is a lipid-conjugated derivative of cytarabine rationally designed to avoid cytarabine resistance associated with decreased cellular uptake.

Study Details

In the trial, 381 patients with relapsed/refractory AML in centers in North America, Europe, and Australia were randomly assigned to elacytarabine 2,000 mg/m2/d as a continuous infusion for 120 hours followed by ≥ 6 days without additional elacytarabine (n = 191) or investigator’s choice of one of seven commonly used AML salvage regimens selected before randomization (n = 190). Investigator’s choice regimens consisted of: cytarabine at 1 to 6 g/m2/d for up to 6 days with a maximum total dose of 36 g/m2 per course; mitoxantrone, etoposide, and cytarabine; fludarabine, cytarabine, and granulocyte colony-stimulating factor (Neupogen) with or without idarubicin; low-dose cytarabine at a maximum dose of 40 mg/d; hypomethylating agents (decitabine or azacitidine); hydroxyurea; or supportive care. The primary endpoint was overall survival.


Median overall survival was 3.5 months in the elacytarabine group vs 3.3 months in the control group (hazard ratio [HR] = 0.97, P =.96). In patients aged ≥ 65 years, median overall survival was 2.9 vs 4.1 months (HR = 1.10, P = .32). There were no significant differences in overall survival among any of the investigator’s choice regimens.

There was no significant difference between elacytarabine and investigator’s choice in relapse-free survival (5.1 vs 3.7 months) or response rate (23% vs 21%). 

As noted by the investigators, “Prolonged survival was only achieved in a few patients in both study arms whose disease responded and who underwent allogeneic stem-cell transplantation.”

The investigators concluded, “Neither elacytarabine nor any of the seven alternative treatment regimens provided clinically meaningful benefit to these patients. [Overall survival] 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.”

Gail J. Roboz, MD, of Weill Cornell Medical College and NewYork-Presbyterian Hospital, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by Clavis Pharma. For full disclosures of the study authors, visit

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