Romidepsin in Japanese patients with relapsed or refractory peripheral T-cell lymphoma: a phase I/II and pharmacokinetics study

Dai Maruyama, Kensei Tobinai, Michinori Ogura, Toshiki Uchida, Kiyohiko Hatake, Masafumi Taniwaki, Kiyoshi Ando, Kunihiro Tsukasaki, Takashi Ishida, Naoki Kobayashi, Kenichi Ishizawa, Yoichi Tatsumi, Koji Kato, Toru Kiguchi, Takayuki Ikezoe, Eric Laille, Tokihiro Ro, Hiromi Tamakoshi, Sanae Sakurai, Tomoko Ohtsu

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/m(2). 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/m(2); n = 6, 14 mg/m(2)) exhibited DLT. In phase II, 40 patients with PTCL were treated with 14 mg/m(2) 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.