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A multicenter, single-arm, Phase II clinical trial of bendamustine monotherapy in patients with chronic lymphocytic leukemia in Japan

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Abstract

The present study was intended to examine the efficacy and safety of bendamustine monotherapy in patients with previously untreated chronic lymphocytic leukemia (CLL) for whom treatment with fludarabine (FLU) was not suitable, and in FLU-naïve patients with relapsed/refractory CLL. We intravenously administered bendamustine 100 mg/m2/day on days 1 and 2 of each 28-day cycle to 10 patients (eight previously untreated; two relapsed/refractory) up to six cycles. The primary endpoint was overall response rate (ORR: partial remission or better) according to the 2008 International Workshop on the CLL guidelines. The ORR was 60.0% (6/10), with the 95% confidence interval of 26.2–87.8%. Neither disease progression nor mortality occurred during follow-up. Therefore, the medians for progression-free survival, duration of response, and overall survival were estimated to exceed 12.6, 8.7, and 12.6 months, respectively. Adverse events (AEs) occurred in all 10 patients. Grade 3/4 hematologic AEs included lymphopenia (90%), neutropenia (80%), CD4 lymphopenia (80%), and leukopenia (70%). Nonhematologic AEs included constipation (80%), nausea (80%), malaise (50%), and anorexia (50%). There was one case each of grade 3 infection and adenocarcinoma of the stomach. Bendamustine showed high efficacy for Japanese patients with previously untreated or relapsed/refractory CLL, and its safety profile was acceptable.

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Acknowledgements

The authors thank patients, investigators, and staff who were involved in the present study. Research support was provided by SymBio Pharmaceuticals. This work was funded by SymBio Pharmaceuticals Ltd and Eisai Co., Ltd. No grant number applies. The authors also manifest our gratitude to the members of the Efficacy and Safety Monitoring Committee—Hirokazu Murakami, MD, PhD, Noriko Usui, MD, PhD, and Keisuke Toyama, MD, PhD, to the members of the Independent Review Committee—Sadao Aoki, MD, PhD, Naoya Nakamura, MD, PhD, and Ukihide Tateishi, MD, PhD, and to the medical advisor—Kazuo Tamura, MD, PhD. Furthermore, the authors thank Satoshi Sakima, MD, for his gracious review of the manuscript.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Yoshiaki Ogawa & Kiyoshi Ando

  2. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Koji Izutsu

  3. Department of Hematology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuyama, Japan

    Toru Kiguchi

  4. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Ilseung Choi

  5. Department of Hematology, Jiaikai Imamura Bun-in Hospital, Kagoshima, Japan

    Yoshifusa Takatsuka

  6. Department of Oncology/Hematology, School of Medicine, Shimane University, Izumo, Japan

    Junji Suzumiya

Authors
  1. Yoshiaki Ogawa
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  2. Koji Izutsu
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  3. Toru Kiguchi
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  4. Ilseung Choi
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  5. Yoshifusa Takatsuka
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  6. Kiyoshi Ando
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  7. Junji Suzumiya
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Japanese Bendamustine CLL Study Group

Corresponding author

Correspondence to Yoshiaki Ogawa.

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Conflict of interest

Dr. Izutsu has received honoraria from Chugai, Kyowa Hakko Kirin, and Takeda; and has received research funding from Kyowa Hakko Kirin, MSD, Celgene, and Pfizer. Dr. Ando has received research funding form Kyowa Hakko Kirin. Dr. Suzumiya has received honoraria from Chugai, Eisai, and Takeda; and has received research funding from Kyowa Hakko Kirin, Chugai, Astellas, and Toyama Chemical. All remaining authors have declared no conflicts of interest.

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Ogawa, Y., Izutsu, K., Kiguchi, T. et al. A multicenter, single-arm, Phase II clinical trial of bendamustine monotherapy in patients with chronic lymphocytic leukemia in Japan. Int J Hematol 105, 631–637 (2017). https://doi.org/10.1007/s12185-016-2178-9

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  • DOI: https://doi.org/10.1007/s12185-016-2178-9

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