Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms.

Abstract

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. One hundred and twenty-one patients, median age 60 (range 21-81) years, were enrolled. In phase 1, cohorts of 6-12 patients were assigned to 12-18 mg/m2/day of mitoxantrone as part of GCLAM. Because all dose levels were well-tolerated, mitoxantrone at 18 mg/m2 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 MRDneg CR rate of 71% (primary phase 2 endpoint). Seven patients achieved a CR with incomplete blood count recovery (CRi; 7%, 5 MRDneg) for a CR/CRi rate of 81/94 (86%). Four-week mortality was 2%. After adjustment, the MRDneg 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 18 mg/m2/day is safe and induces high-quality remissions in adults with newly-diagnosed AML.

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Citation

Published Version (Please cite this version)

10.1038/s41375-018-0135-8

Publication Info

Halpern, Anna B, Megan Othus, Emily M Huebner, Bart L Scott, Pamela S Becker, Mary-Elizabeth M Percival, Paul C Hendrie, Kelda M Gardner, et al. (2018). Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms. Leukemia, 32(11). pp. 2352–2362. 10.1038/s41375-018-0135-8 Retrieved from https://hdl.handle.net/10161/19545.

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Scholars@Duke

Erba

Harry Paul Erba

Professor of Medicine

I am a clinical investigator in the Division of Hematologic Malignancies and Cellular Therapy in the Department of Medicine.  I serve as Director of the Leukemia Program and Director of Phase I Development in Hematologic Malignancies.  I am also the Chair of the SWOG Leukemia Committee.  I am interested in the clinical development of novel therapies for acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative neoplasms (such as chronic myeloid leukemia, polycythemia vera, essential thrombocythemia and myelofibrosis), and acute lymphoblastic leukemia.  Specifically, I have been the Principal Investigator for small molecular inhibitors, antibody-drug conjugates and cytotoxic chemotherapy.  


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