Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid lineage. Outcomes in older patients are poor with high rates of resistant and relapsed disease. Devimistat is a lipoic acid analog that inhibits mitochondrial metabolism. Devimistat combined with high dose cytarabine (HiDAC) and mitoxantrone resulted in promising phase I and II response rates especially in older patients. Therefore, the phase 3 ARMADA 2000 trial was conducted in relapsed or refractory AML patients 50 years of age or older. The study randomized patients between devimistat combined with high-dose cytarabine and mitoxantrone (CHAM) or one of three control treatment regimens without devimistat: high-dose cytarabine and mitoxantrone (HAM); mitoxantrone, etoposide and cytarabine (MEC); or fludarabine, cytarabine, and filgrastim (FLAG). Overall, 265 subjects consented to participate from 56 sites across 11 countries and 200 patients were randomized, 98 patients to the devimistat arm and 102 patients to the control arm. The safety profile was consistent with high dose cytarabine-based salvage regimens. There were 18 (9%) deaths on study (11 CHAM, 7 control). The study failed to meet its primary endpoint with a complete remission rate of 20.4% in the devimistat arm compared to 21.6% in the control arm (p=0.57). Overall survival was not statistically significantly different between arms with a median of 8.9 months in the CHAM arm compared to 6.2 months in the control arm (p=0.62). In conclusion, devimistat added to chemotherapy did not improve the CR rate or survival in relapsed or refractory AML patients 50 years of age or older.

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