title: Safety, efficacy and pharmacokinetics of humanized anti-CD52 monoclonal antibody alemtuzumab in Japanese patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
abstract: OBJECTIVE
  To evaluate the safety, efficacy and pharmacokinetics of alemtuzumab in Japanese patients, we conducted a phase I study in patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
  
  
  METHODS
  Six patients received alemtuzumab by intravenous infusion every other day three times a week for 12 weeks. The dose was gradually escalated on daily basis (3, 10 and then 30 mg) until the patient tolerated. The primary objective was to evaluate the safety of alemtuzumab in Japanese patients and the secondary objectives were to evaluate the overall response rate and the pharmacokinetics.
  
  
  RESULTS
  The major treatment-emergent adverse events were anemia, neutropenia (6/6 patients each) and thrombocytopenia (5/6 patients) in hematologic adverse events, and nausea, vomiting, decreased appetite, cytomegalovirus test positive and pyrexia (4/6 patients) in non-hematologic adverse events. As serious adverse events, cytomegalovirus infection, pulmonary tuberculosis and diffuse large B-cell lymphoma were reported in 1/6 patient each. The overall response rate was 33% (95% confidence interval: 4-78) (1/6 patient each achieved complete response and partial response, respectively) and 3/6 patients had stable disease and 1/6 patient had progressive disease. The median time to response was 2.9 months. After last intravenous dosing (Week 12) of alemtuzumab 30 mg every other day three times a week, Cmax, tmax, AUC0-τand t1/2were higher and CL and Vsswere lower than the values observed after the first dose.
  
  
  CONCLUSIONS
  The efficacy, safety and pharmacokinetics results observed with alemtuzumab in Japanese patients were generally similar to those reported in overseas clinical studies. Alemtuzumab at 30 mg by intravenous infusion every other day three times a week for 12 weeks should be safe and effective similarly in Japanese B-cell chronic lymphocytic leukemia patients.
  
  
  BACKGROUND
  NCT00923182.
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi kishizaw@med.id.yamagata-u.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi.
authors.forename: Noriko
authors.initials: N
authors.lastname: Fukuhara
authors.affiliation: Department of Hematology, Chiba University Graduate School of Medicine, Chiba.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
authors.affiliation: Department of Hematology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Aichi.
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Sanofi K.K., Shinjuku-ku, Tokyo.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Sanofi K.K., Shinjuku-ku, Tokyo.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sunaga
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D019540:Area Under Curve; D044466:Asian People; D000074301:CD52 Antigen; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000209:etiology; D006023:Glycoproteins / Q000276:immunology*; D006207:Half-Life; D006801:Humans; D007564:Japan; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000209:etiology; D012372:ROC Curve; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab
keywords: alemtuzumab; efficacy; pharmacokinetics; relapsed or refractory B-CLL; safety