TY - JOUR
T1 - Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan
AU - Koh, Katsuyoshi
AU - Ogawa, Chitose
AU - Okamoto, Yasuhiro
AU - Kudo, Kazuko
AU - Inagaki, Jiro
AU - Morimoto, Tsuyoshi
AU - Mizukami, Hideya
AU - Ecstein-Fraisse, Evelyne
AU - Kikuta, Atsushi
N1 - Funding Information:
We would like to thank Keizo Horibe and Tomoki Naoe from the Nagoya Medical Center for their assistance with this study. This work was supported by Genzyme Japan K.K. All authors agreed to the content of the manuscript.
Publisher Copyright:
© 2016, The Japanese Society of Hematology.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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/m2/day for 5 days, followed by 52 mg/m2/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m2/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. Cmax and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m2/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.
AB - 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/m2/day for 5 days, followed by 52 mg/m2/day for 5 days in subsequent cycles. Cohort 2 patients were consistently treated with 52 mg/m2/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. Cmax and AUC of clofarabine increased in a dose-dependent fashion, but its elimination half-life (T1/2) did not appear to be dependent on dose or duration of treatment. Clofarabine at 52 mg/m2/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.
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U2 - 10.1007/s12185-016-2004-4
DO - 10.1007/s12185-016-2004-4
M3 - Article
C2 - 27086352
AN - SCOPUS:84963721479
VL - 104
SP - 245
EP - 255
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 2
ER -