International Journal of Hematology

, Volume 89, Issue 5, pp 679–688

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

  • Arinobu Tojo
  • Kensuke Usuki
  • Akio Urabe
  • Yasuhiro Maeda
  • Yukio Kobayashi
  • Itsuro Jinnai
  • Kazuma Ohyashiki
  • Miki Nishimura
  • Tatsuya Kawaguchi
  • Hideo Tanaka
  • Koichi Miyamura
  • Yasushi Miyazaki
  • Timothy Hughes
  • Susan Branford
  • Shinichiro Okamoto
  • Jun Ishikawa
  • Masaya Okada
  • Noriko Usui
  • Hiromi Tanii
  • Taro Amagasaki
  • Hiroko Natori
  • Tomoki Naoe
Original Article

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.

Keywords

Nilotinib CML BCR-ABL Imatinib resistant Ph+ ALL 

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Copyright information

© The Japanese Society of Hematology 2009

Authors and Affiliations

  • Arinobu Tojo
    • 1
  • Kensuke Usuki
    • 2
  • Akio Urabe
    • 2
  • Yasuhiro Maeda
    • 3
  • Yukio Kobayashi
    • 4
  • Itsuro Jinnai
    • 5
  • Kazuma Ohyashiki
    • 6
  • Miki Nishimura
    • 7
  • Tatsuya Kawaguchi
    • 8
  • Hideo Tanaka
    • 9
  • Koichi Miyamura
    • 10
  • Yasushi Miyazaki
    • 11
  • Timothy Hughes
    • 12
  • Susan Branford
    • 12
  • Shinichiro Okamoto
    • 13
  • Jun Ishikawa
    • 14
  • Masaya Okada
    • 15
  • Noriko Usui
    • 16
  • Hiromi Tanii
    • 17
  • Taro Amagasaki
    • 17
  • Hiroko Natori
    • 17
  • Tomoki Naoe
    • 18
  1. 1.The Institute of Medical ScienceThe University of TokyoTokyoJapan
  2. 2.NTT Kanto Medical CenterTokyoJapan
  3. 3.Kinki University School of MedicineOsakaJapan
  4. 4.National Cancer Center HospitalTokyoJapan
  5. 5.International Medical CenterSaitama Medical UniversitySaitamaJapan
  6. 6.Tokyo Medical University HospitalTokyoJapan
  7. 7.Chiba University HospitalChibaJapan
  8. 8.Kumamoto University HospitalKumamotoJapan
  9. 9.Hiroshima University HospitalHiroshimaJapan
  10. 10.Japanese Red Cross Nagoya First HospitalNagoyaJapan
  11. 11.Nagasaki University Hospital of Medicine and DentistryNagasakiJapan
  12. 12.Hanson Institute Centre for CancerAdelaideAustralia
  13. 13.Keio University HospitalTokyoJapan
  14. 14.Osaka University HospitalOsakaJapan
  15. 15.The Hospital of Hyogo College of MedicineHyogoJapan
  16. 16.Jikei University HospitalTokyoJapan
  17. 17.Novartis Pharma JapanTokyoJapan
  18. 18.Nagoya University HospitalAichiJapan

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