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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The authors wish to gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Research reported in this publication was supported by the National Institutes of Health under Award Numbers U10-CA180888, U10-CA180819, and U10-CA180828. A.B.H., S.A.B., and A.A. were supported by a fellowship training grant from the National Heart, Lung, and Blood Institute/National Institutes of Health (T32-HL007093). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A.B.H. is the recipient of a Conquer Cancer Foundation/American Society of Clinical Oncology (ASCO) Young Investigator Award. R.B.W. is a Leukemia & Lymphoma Society Scholar in Clinical Research.

Author information


  1. Clinical Research Division, Fred Hutchinson Cancer Research Center/University of Washington, Seattle, WA, USA

    • Anna B. Halpern
    • , Emily M. Huebner
    • , Bart L. Scott
    • , Pamela S. Becker
    • , Mary-Elizabeth M. Percival
    • , Kaysey F. Orlowski
    • , Frederick R. Appelbaum
    • , Elihu H. Estey
    •  & Roland B. Walter
  2. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA

    • Anna B. Halpern
    • , Pamela S. Becker
    • , Mary-Elizabeth M. Percival
    • , Paul C. Hendrie
    • , Kelda M. Gardner
    • , Elihu H. Estey
    •  & Roland B. Walter
  3. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    • Megan Othus
  4. SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    • Megan Othus
  5. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

    • Bart L. Scott
    •  & Frederick R. Appelbaum
  6. Deparment of Pharmacy Services, University of Washington, Seattle, WA, USA

    • Tara L. Chen
  7. Hematology/Oncology Fellowship Program, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    • Sarah A. Buckley
    •  & Asma Anwar
  8. Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    • Harry P. Erba
  9. Department of Epidemiology, University of Washington, Seattle, WA, USA

    • Roland B. Walter


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Correspondence to Roland B. Walter.

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