Michinori Ogura1, Yoshitaka Imaizumi2, Naokuni Uike3, Norio Asou4, Atae Utsunomiya5, Toshiki Uchida6, Tomohiro Aoki7, Kunihiro Tsukasaki8, Jun Taguchi2, Ilseung Choi9, Dai Maruyama10, Kisato Nosaka11, Nianhang Chen12, Shuichi Midorikawa13, Tomoko Ohtsu13, Kensei Tobinai10. 1. Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Aichi, Japan; Department of Hematology, Tokai Central Hospital, Higashijimacho, Sohara, Kakamigahara, Gifu, Japan. Electronic address: mi-ogura@naa.att.ne.jp. 2. Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan. 3. Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan; Department of Palliative Care, Saga-Ken Medical Centre, Koseikan, Saga, Japan. 4. Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan; Department of Hematology, Saitama Medical University International Medical Center, Saitama, Japan. 5. Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan. 6. Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Aichi, Japan. 7. Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Aichi, Japan; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Aichi, Japan. 8. Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan; Department of Hematology, National Cancer Center Hospital East, Chiba, Japan. 9. Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan. 10. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. 11. Cancer Center, Kumamoto University Hospital, Aichi, Japan; Department of Therapeutics Development and Clinical Research Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan. 12. Celgene Corporation, Summit, NJ, USA. 13. Celgene KK, Tokyo, Japan.
Abstract
BACKGROUND: Patients with adult T-cell leukaemia-lymphoma have few treatment options after relapse and poor survival outcomes with current therapies. We aimed to determine the maximum tolerated dose of lenalidomide, an oral immunomodulator, in Japanese patients with relapsed adult T-cell leukaemia-lymphoma and other peripheral T-cell lymphomas. METHODS: In this phase 1 study, we enrolled patients aged 20 years or older with Eastern Cooperative Oncology Group performance status 0-2, documented diagnosis of aggressive adult T-cell leukaemia-lymphoma or other peripheral T-cell lymphoma subtypes, and at least one previous antilymphoma therapy. Patients were sequentially assigned to lenalidomide 25 mg/day, days 1-21 of a 28-day cycle (cohort 1), 25 mg/day continuously (cohort 2), and 35 mg/day continuously (cohort 3) in a 3 + 3 design. The primary study endpoint was to identify the maximum tolerated dose of lenalidomide. Analyses were performed per protocol for efficacy and in the intent-to-treat patient population for safety. This completed trial is registered with ClinicalTrials.gov, number NCT01169298. FINDINGS: We enrolled 14 patients from six centres in Japan. Of 13 assessable patients (nine with adult T-cell leukaemia-lymphoma, four with other peripheral T-cell lymphomas) receiving lenalidomide, dose-limiting toxic effects were reported in three patients during cycle 1 (one grade 4 thrombocytopenia [cohort 2], one grade 3 QT prolongation on electrocardiogram [cohort 3], and one grade 3 fatigue and grade 4 thrombocytopenia [cohort 3]). The maximum tolerated dose was identified as lenalidomide 25 mg/day given continuously. The most common grade 3 or worse adverse events were neutropenia (eight [62%] patients), lymphopenia (seven [54%] patients), and thrombocytopenia (four [31%] patients); myelosuppression was similar in each cohort. Serious adverse events occurred in eight (62%) patients; thrombocytopenia, which occurred in three (23%) patients, was the only serious adverse event reported in more than one patient. INTERPRETATION: We were able to determine the dose and schedule for lenalidomide treatment in previously treated patients with aggressive, adult T-cell leukaemia-lymphoma. This dose will be used in a subsequent phase 2 study. FUNDING: Celgene Corporation.
BACKGROUND:Patients with adult T-cell leukaemia-lymphoma have few treatment options after relapse and poor survival outcomes with current therapies. We aimed to determine the maximum tolerated dose of lenalidomide, an oral immunomodulator, in Japanese patients with relapsed adult T-cell leukaemia-lymphoma and other peripheral T-cell lymphomas. METHODS: In this phase 1 study, we enrolled patients aged 20 years or older with Eastern Cooperative Oncology Group performance status 0-2, documented diagnosis of aggressive adult T-cell leukaemia-lymphoma or other peripheral T-cell lymphoma subtypes, and at least one previous antilymphoma therapy. Patients were sequentially assigned to lenalidomide 25 mg/day, days 1-21 of a 28-day cycle (cohort 1), 25 mg/day continuously (cohort 2), and 35 mg/day continuously (cohort 3) in a 3 + 3 design. The primary study endpoint was to identify the maximum tolerated dose of lenalidomide. Analyses were performed per protocol for efficacy and in the intent-to-treat patient population for safety. This completed trial is registered with ClinicalTrials.gov, number NCT01169298. FINDINGS: We enrolled 14 patients from six centres in Japan. Of 13 assessable patients (nine with adult T-cell leukaemia-lymphoma, four with other peripheral T-cell lymphomas) receiving lenalidomide, dose-limiting toxic effects were reported in three patients during cycle 1 (one grade 4 thrombocytopenia [cohort 2], one grade 3 QT prolongation on electrocardiogram [cohort 3], and one grade 3 fatigue and grade 4 thrombocytopenia [cohort 3]). The maximum tolerated dose was identified as lenalidomide 25 mg/day given continuously. The most common grade 3 or worse adverse events were neutropenia (eight [62%] patients), lymphopenia (seven [54%] patients), and thrombocytopenia (four [31%] patients); myelosuppression was similar in each cohort. Serious adverse events occurred in eight (62%) patients; thrombocytopenia, which occurred in three (23%) patients, was the only serious adverse event reported in more than one patient. INTERPRETATION: We were able to determine the dose and schedule for lenalidomide treatment in previously treated patients with aggressive, adult T-cell leukaemia-lymphoma. This dose will be used in a subsequent phase 2 study. FUNDING: Celgene Corporation.