Phase 1/2 Trial of GCLAM with Dose-Escalated Mitoxantrone for Newly Diagnosed AML or Other High-Grade Myeloid Neoplasms

Outcomes with “7+3” are often unsatisfactory in acute myeloid leukemia (AML). Trials demonstrating improved outcomes with high-dose cytarabine, addition of cladribine, or escalated anthracycline doses prompted a phase 1/2 study (NCT02044796) of G-CSF, cladribine, high-dose cytarabine, and dose-escalated mitoxantrone (GCLAM) in adults with newly-diagnosed AML or other high-grade myeloid neoplasms. 121 patients, median age 60 (range: 21–81) years, were enrolled. In phase 1, cohorts of 6–12 patients were assigned to 12–18mg/m(2)/day of mitoxantrone as part of GCLAM. Because all dose levels were well-tolerated, mitoxantrone at 18mg/m(2) was declared the recommended phase 2 dose (RP2D). 74/94 (79%) patients treated at the RP2D achieved a complete remission (CR; 67/74 without measureable residual disease [MRD]) for an overall MRD(neg) CR rate of 71% (primary phase 2 endpoint). Seven patients achieved a CR with incomplete blood count recovery (CRi; 7%, 5 MRD(neg)) for a CR/CRi rate of 81/94 (86%). 4-week mortality was 2%. After adjustment, the MRD(neg) CR and CR/CRi rates compared favorably to 100 matched controls treated with 7+3 at our center and 245 matched patients treated with 7+3 on a cooperative group trial. Our data indicate GCLAM with mitoxantrone at 18mg/m(2)/day is safe and induces high-quality remissions in adults with newly-diagnosed AML.