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 AmagasakiHiroko Natori, Tomoki Naoe

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)679-688
Number of pages10
JournalInternational journal of hematology
Volume89
Issue number5
DOIs
Publication statusPublished - 2009 Jun 1

Keywords

  • BCR-ABL
  • CML
  • Imatinib resistant
  • Nilotinib
  • Ph+ ALL

ASJC Scopus subject areas

  • Hematology

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