Devimistat plus chemotherapy vs chemotherapy alone for older relapsed or refractory patients with AML: results of the ARMADA trial.

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 and mitoxantrone resulted in promising phase 1 and 2 response rates especially in older patients. Therefore, the phase 3 ARMADA 2000 trial was conducted in patients aged ≥50 years with relapsed or refractory AML. The study randomized patients between devimistat combined with high-dose cytarabine and mitoxantrone (CHAM) or 1 of 3 control treatment regimens without devimistat: high-dose cytarabine and mitoxantrone; mitoxantrone, etoposide, and cytarabine; or fludarabine, cytarabine, and filgrastim. Overall, 265 patients 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 on CHAM and 7 on control). The study failed to meet its primary end point, with a complete remission (CR) rate of 20.4% in the devimistat arm compared with 21.6% in the control arm ( = .57). Overall survival was not statistically significantly different between the study arms, with a median of 8.9 months in the CHAM arm compared with 6.2 months in the control arm ( = .62). In conclusion, devimistat added to chemotherapy did not improve the CR rate or survival in patients aged ≥50 years with relapsed or refractory AML. This trial was registered at www.ClinicalTrials.gov as #NCT03504410.