Randomized phase III trial comparing Daunorubicin and ara-C (DA) versus ara-C, Daunorubicin, and Etoposide (ADE) as induction chemotherapy in pediatric acute myeloid leukemia (InPOG-AML-16-01)

Abstract

Background: The benefit of three-drug induction chemotherapy over a two-drug induction has not been evaluated in pediatric acute myeloid leukemia (AML). We, therefore, conducted a multi-center, phase III trial to ascertain the benefit of a three-drug induction regimen in pediatric AML. Methods: Patients aged between 1-18 years with newly diagnosed AML were randomized to two cycles of induction chemotherapy with daunorubicin and ara-C (DA) or two cycles of ara-C, daunorubicin, and etoposide (ADE). After completing the induction, patients in both arms received consolidation with two cycles of high-dose ara-C. The study's primary objective was to compare the event-free survival (EFS) between the two arms. The secondary objectives were to compare the complete remission (CR) rates, overall survival (OS), and toxicities. Results: The study randomized 149 patients, 77 in the DA and 72 in the ADE arm. The median age was 8.7 years, and 92 (62%) patients were males. The median follow-up was 50.9 months. The CR rate in the DA and ADE arm were 82% and 79% (p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm (p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively (p = 0.66). The 5-year OS in the DA and ADE arm was 41.4% and 42.09%, respectively (p = 0.74). There were no significant differences in toxicities between the regimens. Conclusions: There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric patients with AML