title: Lenalidomide in relapsed adult T-cell leukaemia-lymphoma or peripheral T-cell lymphoma (ATLL-001): a phase 1, multicentre, dose-escalation study.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Celgene Corporation.
authors.affiliation: 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.
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imaizumi
authors.affiliation: Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan; Department of Palliative Care, Saga-Ken Medical Centre, Koseikan, Saga, Japan.
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.affiliation: Department of Hematology, Kumamoto University Hospital, Kumamoto, Japan; Department of Hematology, Saitama Medical University International Medical Center, Saitama, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Asou
authors.affiliation: Department of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan.
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Aichi, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchida
authors.affiliation: 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.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan; Department of Hematology, National Cancer Center Hospital East, Chiba, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsukasaki
authors.affiliation: Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Taguchi
authors.affiliation: Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Maruyama
authors.affiliation: 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.
authors.forename: Kisato
authors.initials: K
authors.lastname: Nosaka
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Nianhang
authors.initials: N
authors.lastname: Chen
authors.affiliation: Celgene KK, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Midorikawa
authors.affiliation: Celgene KK, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohtsu
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D000077269:Lenalidomide; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000139:chemically induced; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide