Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma

Michinori Ogura, Kensei Tobinai, Kiyohiko Hatake, Kenichi Ishizawa, Naokuni Uike, Toshiki Uchida, Tatsuya Suzuki, Tomohiro Aoki, Takashi Watanabe, Dai Maruyama, Masahiro Yokoyama, Takatoshi Takubo, Hideaki Kagehara, Takafumi Matsushima

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    33 Citations (Scopus)

    Abstract

    Brentuximab vedotin is an antibody-drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4-16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650). This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma.

    Original languageEnglish
    Pages (from-to)840-846
    Number of pages7
    JournalCancer science
    Volume105
    Issue number7
    DOIs
    Publication statusPublished - 2014 Jul

    Keywords

    • Anaplastic large cell lymphoma
    • Brentuximab vedotin
    • Clinical trial
    • Hodgkin's lymphoma
    • Japanese patients

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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