title: Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan.
abstract: A phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), efficacy and pharmacogenetic characteristics of clofarabine in seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL). Patients in Cohort 1 received clofarabine 30 mg/m(2)/day for 5 days, followed by 52 mg/m(2)/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m(2)/day for 5 days. No more than six cycles were performed. Every patient had at least one ≥Grade 3 adverse event (AE). AEs (≥Grade 3) related to clofarabine were anaemia, neutropenia, febrile neutropenia, thrombocytopenia, alanine aminotransferase increased, aspartate aminotransferase increased, haemoglobin decreased, and platelet (PLT) count decreased. C max and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T 1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m(2)/day shows similarly tolerable safety and PK profiles compared to those in previous studies. No complete remission (CR), CR without PLT recovery, or partial remission was observed. Since clofarabine is already used as a key drug for relapsed/refractory ALL patients in many countries, the efficacy of clofarabine in Japanese pediatric patients should be evaluated in larger study including more patients, such as by post-marketing surveillance.
authors.affiliation: Department of Hematology/Oncology, Saitama Children's Medical Center, 2100 Magome, Iwatsuki Ward, Saitama City, Saitama Prefecture, 339-0077, Japan. ko.katsuyoshi@pref.saitama.lg.jp.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Koh
authors.affiliation: Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan.|Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Chitose
authors.initials: C
authors.lastname: Ogawa
authors.affiliation: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Hematology/Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.|Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Inagaki
authors.affiliation: Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Sanofi K.K., Tokyo, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Sanofi K.K., Tokyo, Japan.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ecstein-Fraisse
authors.affiliation: Department of Pediatric Oncology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kikuta
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000293:Adolescent; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D000077866:Clofarabine
keywords: Acute lymphoblastic leukemia; Children; Clofarabine; Phase 1