title: 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.
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).
authors.affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Aoki
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Dai
authors.initials: D
authors.lastname: Maruyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Takubo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagehara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Matsushima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D000079963:Brentuximab Vedotin; D004334:Drug Administration Schedule; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017730:Ki-1 Antigen / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy*; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates; D017730:Ki-1 Antigen; D000079963:Brentuximab Vedotin
keywords: Anaplastic large cell lymphoma; Hodgkin's lymphoma; Japanese patients; brentuximab vedotin; clinical trial