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A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL

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Abstract

Nilotinib is a second-generation BCR-ABL kinase inhibitor with improved potency and selectivity compared to imatinib. A Phase I/II dose-escalation study was designed to evaluate the efficacy, safety, and pharmacokinetics of nilotinib in Japanese patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL). A total of 34 patients were evaluated in this analysis and had a median duration of drug exposure of 293 (range 13–615) days. All 6 CML-CP patients without complete hematologic response (CHR) at baseline rapidly achieved CHR. A major cytogenetic response was achieved in 94% of patients with CML-CP, including a complete cytogenetic response in 69%. A major molecular response was achieved by 56%. These responses were also observed in patients with CML in advanced stages and Ph+ ALL. Non-hematologic adverse events were mostly mild to moderate. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 50 and 28% of patients, respectively. Overall, the results of this study suggest that nilotinib induced significant responses in imatinib-resistant or -intolerant patients with CML-CP and CML in advanced stages and Ph+ ALL. The results of this study confirmed the efficacy and safety of nilotinib in Japanese patients.

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Authors and Affiliations

  1. The Institute of Medical Science, The University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo, Japan

    Arinobu Tojo

  2. NTT Kanto Medical Center, Tokyo, Japan

    Kensuke Usuki & Akio Urabe

  3. Kinki University School of Medicine, Osaka, Japan

    Yasuhiro Maeda

  4. National Cancer Center Hospital, Tokyo, Japan

    Yukio Kobayashi

  5. International Medical Center, Saitama Medical University, Saitama, Japan

    Itsuro Jinnai

  6. Tokyo Medical University Hospital, Tokyo, Japan

    Kazuma Ohyashiki

  7. Chiba University Hospital, Chiba, Japan

    Miki Nishimura

  8. Kumamoto University Hospital, Kumamoto, Japan

    Tatsuya Kawaguchi

  9. Hiroshima University Hospital, Hiroshima, Japan

    Hideo Tanaka

  10. Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koichi Miyamura

  11. Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan

    Yasushi Miyazaki

  12. Hanson Institute Centre for Cancer, Adelaide, Australia

    Timothy Hughes & Susan Branford

  13. Keio University Hospital, Tokyo, Japan

    Shinichiro Okamoto

  14. Osaka University Hospital, Osaka, Japan

    Jun Ishikawa

  15. The Hospital of Hyogo College of Medicine, Hyogo, Japan

    Masaya Okada

  16. Jikei University Hospital, Tokyo, Japan

    Noriko Usui

  17. Novartis Pharma Japan, Tokyo, Japan

    Hiromi Tanii, Taro Amagasaki & Hiroko Natori

  18. Nagoya University Hospital, Aichi, Japan

    Tomoki Naoe

Authors
  1. Arinobu Tojo
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  2. Kensuke Usuki
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  3. Akio Urabe
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  4. Yasuhiro Maeda
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  5. Yukio Kobayashi
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  6. Itsuro Jinnai
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  7. Kazuma Ohyashiki
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  8. Miki Nishimura
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  9. Tatsuya Kawaguchi
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  10. Hideo Tanaka
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  11. Koichi Miyamura
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  12. Yasushi Miyazaki
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  13. Timothy Hughes
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  14. Susan Branford
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  15. Shinichiro Okamoto
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  16. Jun Ishikawa
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  17. Masaya Okada
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  18. Noriko Usui
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  19. Hiromi Tanii
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  20. Taro Amagasaki
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  21. Hiroko Natori
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  22. Tomoki Naoe
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Corresponding author

Correspondence to Arinobu Tojo.

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Tojo, A., Usuki, K., Urabe, A. et al. A Phase I/II study of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL. Int J Hematol 89, 679–688 (2009). https://doi.org/10.1007/s12185-009-0327-0

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  • DOI: https://doi.org/10.1007/s12185-009-0327-0

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