Phase 2 Trial of 3 Novel Regimens for Relapsed/Refractory Acute Myeloid Leukemia

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A combination of alvocidib, cytarabine, and mitoxantron was found to outperform other novel treatments for relapsed/refractory acute myeloid leukemia.
A combination of alvocidib, cytarabine, and mitoxantron was found to outperform other novel treatments for relapsed/refractory acute myeloid leukemia.

Results from a phase 2 trial published in the American Journal of Hematology showed that a combination of alvocidib, cytarabine, and mitoxantrone (FLAM) outperformed 2 alternative regimens for the treatment of relapsed/refractory acute myeloid leukemia (AML).

Researchers sought to improve the outcomes of patients with relapsed/refractory AML by assessing 3 novel regimens: carboplatin and topotecan (CT) for 5 days of continuous infusion each; FLAM in a timed sequential regimen; and sirolimus combined with mitoxantrone, etoposide, and cytarabine (S-MEC). Each arm consisted of a Simon two-stage design.

Ninety patients who were in their first relapse or were refractory to induction/reinduction chemotherapy were included in the study and randomly assigned to 1 of the 3 regimens. Patients in the FLAM arm (median age, 62 years) were older than those in the other 2 arms (median age, 55 years in both). The overall response was highest at 28% in the FLAM arm (10/36 patients, 90% CI: 16%-43%), followed by 16% in the S-MEC arm (3/19 patients, 90% CI: 4%-36%), and 14% in the CT arm (5/35 patients, 90% CI: 7%-35%).

Nine treatment-related deaths occurred. Seven of these deaths were in the FLAM arm, including 4 in elderly patients. In total, 72 patients experienced grade 3 or higher adverse events. The most common hematologic events were cytopenias; others included infections, gastrointestinal toxicity, and metabolic abnormalities.

The authors concluded that “the FLAM regimen had an encouraging response rate and should be considered for further clinical development but should be used with caution in elderly patients.”

Reference

1. Litzow MR, Wang X V., Carroll MP, et al. A randomized trial of three novel regimens for recurrent acute myeloid leukemia demonstrates the continuing challenge of treating this difficult disease [published online October 29, 2018]. Am J Hematol. doi: 10.1002/ajh.25333

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