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


    • The Institute of Medical ScienceThe University of Tokyo
  • Kensuke Usuki
    • NTT Kanto Medical Center
  • Akio Urabe
    • NTT Kanto Medical Center
  • Yasuhiro Maeda
    • Kinki University School of Medicine
  • Yukio Kobayashi
    • National Cancer Center Hospital
  • Itsuro Jinnai
    • International Medical CenterSaitama Medical University
  • Kazuma Ohyashiki
    • Tokyo Medical University Hospital
  • Miki Nishimura
    • Chiba University Hospital
  • Tatsuya Kawaguchi
    • Kumamoto University Hospital
  • Hideo Tanaka
    • Hiroshima University Hospital
  • Koichi Miyamura
    • Japanese Red Cross Nagoya First Hospital
  • Yasushi Miyazaki
    • Nagasaki University Hospital of Medicine and Dentistry
  • Timothy Hughes
    • Hanson Institute Centre for Cancer
  • Susan Branford
    • Hanson Institute Centre for Cancer
  • Shinichiro Okamoto
    • Keio University Hospital
  • Jun Ishikawa
    • Osaka University Hospital
  • Masaya Okada
    • The Hospital of Hyogo College of Medicine
  • Noriko Usui
    • Jikei University Hospital
  • Hiromi Tanii
    • Novartis Pharma Japan
  • Taro Amagasaki
    • Novartis Pharma Japan
  • Hiroko Natori
    • Novartis Pharma Japan
  • Tomoki Naoe
    • Nagoya University Hospital
Original Article

DOI: 10.1007/s12185-009-0327-0

Cite this article as:
Tojo, A., Usuki, K., Urabe, A. et al. Int J Hematol (2009) 89: 679. doi:10.1007/s12185-009-0327-0


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.


NilotinibCMLBCR-ABLImatinib resistantPh+ ALL

Copyright information

© The Japanese Society of Hematology 2009