Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms.
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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.
Antineoplastic Combined Chemotherapy Protocols
Aged, 80 and over
Leukemia, Myeloid, Acute
Published Version (Please cite this version)10.1038/s41375-018-0135-8
Publication InfoHalpern, Anna B; Othus, Megan; Huebner, Emily M; Scott, Bart L; Becker, Pamela S; Percival, Mary-Elizabeth M; ... Walter, Roland B (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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Instructor in the Department 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 v