Mitoxantrone, Etoposide, and Cytarabine (MEC) Following Epigenetic Priming with Decitabine in Adults with Relapsed/Refractory Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms: A Phase 1/2 Study

DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide, and cytarabine following “priming” with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 [range: 19-72] years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well-tolerated. As response rates appeared similar with 7 and 10-days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea, and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC and G-CLAM). Thus, while meeting the pre-specified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.