Romidepsin in Japanese patients with relapsed or refractory peripheral T-cell lymphoma: a phase I/II and pharmacokinetics study
This phase I/II multicenter study evaluated romidepsin treatment in Japanese patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Patients aged ≥20 years received romidepsin via a 4-h intravenous infusion on days 1, 8, and 15 of each 28-day cycle. Phase I used a 3 + 3 design to identify any dose-limiting toxicity (DLT) for regimens of romidepsin 9 and 14 mg/m2. The primary endpoints for phase I and II were DLT and overall response rate (ORR), respectively. Intent-to-treat patients were those who received ≥1 romidepsin dose (PTCL, n = 48; CTCL, n = 2). In phase I, none of the patients (n = 3, 9 mg/m2; n = 6, 14 mg/m2) exhibited DLT. In phase II, 40 patients with PTCL were treated with 14 mg/m2 romidepsin. The most common treatment-emergent grade ≥3 adverse events were lymphopenia (74%), neutropenia (54%), leukopenia (46%), and thrombocytopenia (38%). Patients in phase II showed a 43% ORR, including 25% complete responses. Median progression-free survival was 5.6 months and median duration of response was 11.1 months. This phase I/II study identified a well-tolerated dose of romidepsin, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with relapsed/refractory PTCL.
ClinicalTrials.gov Identifier NCT01456039.
KeywordsCutaneous T-cell lymphoma Japanese Peripheral T-cell lymphoma Relapsed or refractory Romidepsin
All authors performed and/or designed the research study, analyzed the data, contributed to the development and revision of the manuscript, and approved the final version for submission. The authors thank the patients, their family members, and collaborators from participating institutions and Celgene Corporation. Thank you to Norio Komatsu, M.D., Ph.D., for providing medical expertise; Kazuma Ohyashiki, M.D., Ph.D., Jin Takeuchi, M.D., Ph.D., and Noriko Usui, M.D., who served on the efficacy and safety evaluation committee (ESEC); Takashi Terauchi, M.D., Ukihide Tateishi, M.D., and Mitsuaki Tatsumi, M.D., who served on the Independent Radiological Review Committee (IRRC); Yoshihiro Matsuno, M.D., Ph.D., Akiko Maeshima, M.D., Ph.D., and Kouichi Ohshima, M.D., Ph.D., who were the central pathologists for the study; Masaaki Shoji, M.D., who was the cardiologist for the study; and Junji Suzumiya, M.D., Ph.D., who served as an independent efficacy reviewer. Medical writing support was provided by Bio Connections LLC, and funded by Celgene Corporation; the authors were fully responsible for content and editorial decisions for this manuscript.
Compliance with ethical standards
Conflict of interest
D.M. reports personal fees from Celgene during the conduct of the study; and outside the submitted work, honoraria and research funding from Takeda, Janssen, Eisai, Celgene, Kyowa Hakko Kirin, Ono, Mundipharma, and Chugai; research funding from GlaxoSmithKline, Servier, AbbVie, and MSD; and honoraria from Biomedis International, sanofi, Fujifilm, and Mochida Pharmaceutical Co. Ltd. K.To. reports grants and personal fees from Eisai, Takeda, Mundipharma, Kyowa Hakko Kirin, and Celgene; personal fees from HUYA Bioscience International during the conduct of the study; and outside the submitted work, personal fees from Zenyaku Kogyo; grants and personal fees from Janssen, Chugai Pharma, and Ono Pharmaceutical; and grants from GlaxoSmithKline, Servier, and AbbVie. M.O. reports research funding from SymBio and Celltrion; honoraria from AstraZeneca, Takeda, and Celgene; and advisory board personal fees from Mundipharma, MeijiSeika Pharma, and Celltrion outside of the submitted work. K.H. reports relationships/conditions/circumstances that may influence this work from AbbVie, Gilead, Celgene, Solasia, Pfizer, BMS, Janssen, Ono, and Chugai. K.Ts. reports grants from Celgene, Takeda, MundiPharma, and Chugai; and personal lecture fees from Zennyakukogyo, HUYA Biosciences, Chugai, and Kyowa Kirin outside of the submitted work. T.Is. reports personal fees from Celgene K.K. during the conduct of the study; and outside of the submitted work grants from Kyowa Hakko Kirin Co. Ltd, Bayer Pharma AG, and J-pharma Co. Ltd; and honoraria from Kyowa Hakko Kirin Co. Ltd. K.Is. reports grants and personal fees from Kyowa Kirin and Takeda during the conduct of the study; and personal fees from Cyugai, Janssen, Novartis, Ono, and Pfizer outside the submitted work. E.L., T.R., H.T., S.S., and T.O. are employed by and have received stock ownership from Celgene Corporation. T.U., K.A., M.T., N.K., Y.T., K.K., T.K., and T.Ik., have no relevant financial relationships to disclose. The study was designed under the responsibility of Celgene Corporation; the study was funded by Celgene K. K. (Tokyo, Japan); Romidepsin was provided by Celgene K.K. (Tokyo, Japan). Celgene K. K. (Tokyo, Japan) collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.
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