title: Phase I study of clofarabine in adult patients with acute myeloid leukemia in Japan.
abstract: OBJECTIVE
  There are limited treatment options for relapsed/refractory acute myeloid leukemia patients or previously untreated elderly (≥60 years) patients with acute myeloid leukemia. In Phase II studies from the USA and Europe, single-agent clofarabine demonstrated activity and acceptable toxicity in elderly patients with previously untreated acute myeloid leukemia. This Phase I, multicenter study assessed the maximum-tolerated dose, safety, pharmacokinetics and efficacy of clofarabine in Japanese adults with acute myeloid leukemia.
  
  
  METHODS
  Intravenous clofarabine (20, 30 and 40 mg/m(2)/day) was administered for 5 days to Japanese adult patients with relapsed or refractory acute myeloid leukemia or elderly patients with newly diagnosed acute myeloid leukemia.
  
  
  RESULTS
  Fourteen patients, median age of 67.5 (59-72) years, were enrolled in this study. Eleven out of 14 patients had relapsed/refractory acute myeloid leukemia. Three patients received clofarabine at 20 mg/m(2), six at 30 mg/m(2) and five at 40 mg/m(2). Frequently reported treatment-related adverse events included thrombocytopenia (100%), anemia (93%), neutropenia (86%), nausea (86%), alanine aminotransferase increase (71%), headache (71%) and febrile neutropenia (57%). Three patients experienced reversible dose-limiting toxicities; two had increased alanine aminotransferase with 30 and 40 mg/m(2) and one had Grade 3 elevation of serum amylase with 40 mg/m(2). The maximum-tolerated dose was 30 mg/m(2)/day. Cmax and exposure area under the curve0-24h increased with increasing dose and were proportional to dose through the tested dose range. Among the 14 assessable patients, four (29%) achieved complete remission and two (14%) complete remission without platelet recovery. The overall remission rate was 43%.
  
  
  CONCLUSIONS
  These results demonstrate safety and preliminary, promising activity of clofarabine in Japanese patients with acute myeloid leukemia. Further investigation is warranted.
authors.affiliation: *Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, 2-9 Myoken-cho, Showa-ku, Nagoya 466-8650 Japan. mi-ogura@naa.att.ne.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kakihana
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Miyata
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tabata
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000681:Amylases / Q000097:blood; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D001853:Bone Marrow / Q000187:drug effects; D000077866:Clofarabine; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine; D000410:Alanine Transaminase; D000681:Amylases
keywords: Phase I; acute; aged; clinical trial; clofarabine; myeloid leukemia