Original Article

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 TojoAffiliated withThe Institute of Medical Science, The University of Tokyo Email author 
  • , Kensuke UsukiAffiliated withNTT Kanto Medical Center
  • , Akio UrabeAffiliated withNTT Kanto Medical Center
  • , Yasuhiro MaedaAffiliated withKinki University School of Medicine
  • , Yukio KobayashiAffiliated withNational Cancer Center Hospital
  • , Itsuro JinnaiAffiliated withInternational Medical Center, Saitama Medical University
  • , Kazuma OhyashikiAffiliated withTokyo Medical University Hospital
  • , Miki NishimuraAffiliated withChiba University Hospital
  • , Tatsuya KawaguchiAffiliated withKumamoto University Hospital
    • , Hideo TanakaAffiliated withHiroshima University Hospital
    • , Koichi MiyamuraAffiliated withThe Institute of Medical Science, The University of TokyoJapanese Red Cross Nagoya First Hospital
    • , Yasushi MiyazakiAffiliated withThe Institute of Medical Science, The University of TokyoNagasaki University Hospital of Medicine and Dentistry
    • , Timothy HughesAffiliated withThe Institute of Medical Science, The University of TokyoHanson Institute Centre for Cancer
    • , Susan BranfordAffiliated withThe Institute of Medical Science, The University of TokyoHanson Institute Centre for Cancer
    • , Shinichiro OkamotoAffiliated withThe Institute of Medical Science, The University of TokyoKeio University Hospital
    • , Jun IshikawaAffiliated withThe Institute of Medical Science, The University of TokyoOsaka University Hospital
    • , Masaya OkadaAffiliated withThe Institute of Medical Science, The University of TokyoThe Hospital of Hyogo College of Medicine
    • , Noriko UsuiAffiliated withThe Institute of Medical Science, The University of TokyoJikei University Hospital
    • , Hiromi TaniiAffiliated withThe Institute of Medical Science, The University of TokyoNovartis Pharma Japan
    • , Taro AmagasakiAffiliated withThe Institute of Medical Science, The University of TokyoNovartis Pharma Japan
    • , Hiroko NatoriAffiliated withThe Institute of Medical Science, The University of TokyoNovartis Pharma Japan
    • , Tomoki NaoeAffiliated withThe Institute of Medical Science, The University of TokyoNagoya University Hospital

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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.

Keywords

Nilotinib CML BCR-ABL Imatinib resistant Ph+ ALL