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Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia

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Abstract

Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study entry was 5, 7, and 7 years old, respectively. Two patients had hyperdiploid B-precursor ALL, and one had T cell ALL. Although all patients experienced grade 3–4 hematologic toxicity and grade 3 elevation of aminotransferases, no dose-limiting toxicities were observed. The maximum tolerated dose was defined as 1.3 mg/m2. Peripheral neuropathy and respiratory complications were not observed. Complete remission was achieved in all three patients. The mean maximum plasma concentration and area under the concentration–time curve was 74.0 ng/mL and 73.9 ng h/mL, respectively. Thus, adding BZM to 5-drug induction chemotherapy appears safe and well-tolerated in Japanese children with relapsed ALL.

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Acknowledgements

This trial was supported by AMED under Grant number JP17ck0106110. We thank all the patients, families, and investigators who participated in this trial.

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Authors and Affiliations

  1. Department of Pediatrics, St. Luke’s International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan

    Daisuke Hasegawa, Yuri Yoshimoto, Shunsuke Kimura, Tadashi Kumamoto & Atsushi Manabe

  2. Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan

    Tadashi Kumamoto & Chitose Ogawa

  3. Department of Pediatrics, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Naoko Maeda

  4. Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Japan

    Junichi Hara

  5. Department of Pediatric Oncology, Fukushima Medical University Hospital, Fukushima, Japan

    Atsushi Kikuta

  6. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Akiko Kada, Yuka Iijima-Yamashita, Akiko M. Saito & Keizo Horibe

  7. Department of Pharmacy, Tokyo Women’s Medical University Hospital, Tokyo, Japan

    Toshimi Kimura

Authors
  1. Daisuke Hasegawa
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  2. Yuri Yoshimoto
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  3. Shunsuke Kimura
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  4. Tadashi Kumamoto
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  5. Naoko Maeda
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  6. Junichi Hara
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  7. Atsushi Kikuta
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  8. Akiko Kada
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  9. Toshimi Kimura
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  10. Yuka Iijima-Yamashita
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  11. Akiko M. Saito
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  12. Keizo Horibe
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  13. Atsushi Manabe
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  14. Chitose Ogawa
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Contributions

DH collected samples and data, analyzed data and wrote the manuscript; YY, SK, and TD collected samples and data and analyzed data; NM, JH, AtK, and KH analyzed data and gave conceptual advice; AkK performed the statistical analysis and wrote the manuscript. TK performed pharmacokinetic analyses; YIY performed minimal residual disease analyses; AMS performed data management and monitoring during this trial; AM analyzed data, gave conceptual advice, and wrote the manuscript; CO contributed to the conception and design of this study. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Daisuke Hasegawa.

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The authors declare no conflict of interest.

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Hasegawa, D., Yoshimoto, Y., Kimura, S. et al. Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia. Int J Hematol 110, 627–634 (2019). https://doi.org/10.1007/s12185-019-02714-x

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  • DOI: https://doi.org/10.1007/s12185-019-02714-x

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