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Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan

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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/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. 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/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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Acknowledgments

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.

Author information

Author notes

  1. Chitose Ogawa

    Present address: Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan

  2. Kazuko Kudo

    Present address: Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan

Authors and Affiliations

  1. Department of Hematology/Oncology, Saitama Children’s Medical Center, 2100 Magome, Iwatsuki Ward, Saitama City, Saitama Prefecture, 339-0077, Japan

    Katsuyoshi Koh

  2. Department of Pediatrics, St. Luke’s International Hospital, Tokyo, Japan

    Chitose Ogawa

  3. Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Yasuhiro Okamoto

  4. Department of Hematology/Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan

    Kazuko Kudo

  5. Department of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    Jiro Inagaki

  6. Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan

    Tsuyoshi Morimoto

  7. Sanofi K.K., Tokyo, Japan

    Hideya Mizukami & Evelyne Ecstein-Fraisse

  8. Department of Pediatric Oncology, Fukushima Medical University, Fukushima, Japan

    Atsushi Kikuta

Authors
  1. Katsuyoshi Koh
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  2. Chitose Ogawa
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Corresponding author

Correspondence to Katsuyoshi Koh.

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Conflict of interest

HM and EEF are employees of Sanofi K.K., Tokyo, Japan. The other authors declare no conflicts of interest.

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Koh, K., Ogawa, C., Okamoto, Y. et al. Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan. Int J Hematol 104, 245–255 (2016). https://doi.org/10.1007/s12185-016-2004-4

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  • DOI: https://doi.org/10.1007/s12185-016-2004-4

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