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Chronic Myeloproliferative Neoplasias

MK-0457, an Aurora kinase and BCR–ABL inhibitor, is active in patients with BCR–ABL T315I leukemia

Leukemia volume 27, pages 113–117 (2013)Cite this article

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Abstract

MK-0457, an Aurora kinase and BCR–ABL inhibitor, was studied on a Phase I/II study in 77 patients with refractory hematologic malignancies. The average number of cycles per patient was 3 (range 1–21). Maximum tolerated doses for a 5-day short infusion and continuous infusion regimens were 40 mg/m2/h and 144 mg/m2/h, respectively. Drug-related adverse events (AEs) included transient mucositis and alopecia. Eight of 18 patients with BCR–ABL T315I-mutated chronic myelogenous leukemia (44%) had hematologic responses and one of three patients (33%) with Philadelphia chromosome-positive acute lymphoblastic leukemia obtained complete remission. MK-0457 has important activity in patients with leukemias expressing the highly resistant T315I BCR–ABL mutation.

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Acknowledgements

We acknowledge the study coordinators, nurses and physicians who contributed to this study, and the patients and their families for their participation. We thank Boyd Scott for editorial assistance. The research of Francis Giles, Arnon Nagler, Andreas Hochhaus, Oliver G Ottmann, David Rizzieri, Moshe Talpaz, Philipp Le Coutre and Jorge Cortes was funded by Merck.

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Authors and Affiliations

  1. HRB Clinical Research Facilities, National University of Ireland Galway and Trinity College Dublin, Galway, Ireland

    F J Giles

  2. Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

    R T Swords

  3. Chaim Sheba Medical Center, Tel-Hashomer, Israel

    A Nagler

  4. Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

  5. Johann Wolfgang Goethe Universität, Frankfurt, Germany

    O G Ottmann

  6. Division of Cellular Therapy, Duke University Hospital, Durham, NC, USA

    D A Rizzieri

  7. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA

    M Talpaz

  8. Merck & Co., Inc., North Wales, PA, USA

    J Clark, P Watson, A Xiao, B Zhao, D Bergstrom & S J Freedman

  9. Hematology and Oncology Department, Charité, Berlin, Germany

    P D Le Coutre

  10. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    J E Cortes

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  1. F J Giles
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Correspondence to F J Giles.

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Competing interests

Employment or leadership position: Jason Clark, Patricia Watson, Alan Xiao, Baiteng Zhao, Donald Bergstrom, Steven J Freedman—Merck. The remaining authors declare no conflict of interest.

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Author Contributions

Conception and design: Francis Giles, Arnon Nagler, Andreas Hochhaus, Oliver G. Ottmann, David Rizzieri, Moshe Talpaz, Donald Bergstrom, Philipp Le Coutre, Steven J. Freedman, Jorge Cortes. Collection and assembly of data: all authors. Manuscript writing: all authors. Final approval of manuscript: all authors. Provision of study materials or patients: Francis Giles, Arnon Nagler, Andreas Hochhaus, Oliver G. Ottmann, David Rizzieri, Moshe Talpaz, Philipp Le Coutre, Jorge Cortes.

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Giles, F., Swords, R., Nagler, A. et al. MK-0457, an Aurora kinase and BCR–ABL inhibitor, is active in patients with BCR–ABL T315I leukemia. Leukemia 27, 113–117 (2013). https://doi.org/10.1038/leu.2012.186

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