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Ofatumumab combined with chlorambucil for previously untreated chronic lymphocytic leukemia: a phase I/II, open-label study in Japan

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Abstract

Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated CLL who were inappropriate for fludarabine-based therapy. Ten patients were enrolled and treated in this study, all of whom received at least one dose of the study drugs. The tolerability of the treatment was confirmed initially with three patients. The overall response rate was 50%, as determined by the Independent Review Committee (IRC) with computerized tomography. All patients were alive at follow-up, and only one patient had progressive disease. The most common treatment-related adverse events (AEs) were thrombocytopenia (n = 10), neutropenia (n = 9) and rash (n = 6). One grade 3 serious AE related to the study drug occurred (hypoxia). The results indicate that ofatumumab combined with chlorambucil is an effective treatment for Japanese CLL patients, with a manageable safety profile.

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Acknowledgements

This study was funded by GlaxoSmithKline and Genmab. Medical writing assistance was provided by John D. Gibbins, Ph.D., of Edanz Group Japan K.K., and was funded by Novartis Pharma K.K. We thank the patients and their family members, and the doctors, nurses, clinical research coordinators, and the staff of GlaxoSmithKline Japan, Aspen and Genmab.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Kiyohiko Hatake

  2. Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Aichi, Japan

    Michinori Ogura

  3. Department of Hematology, Tokai Central Hospital, Kakamigahara, Gifu, Japan

    Michinori Ogura

  4. Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan

    Kohichi Takada

  5. Division of Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Masafumi Taniwaki

  6. Novartis Pharma K.K., Tokyo, Japan

    Fanghong Zhang & Taizo Fujita

  7. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Kanagawa, Japan

    Kiyoshi Ando

Authors
  1. Kiyohiko Hatake
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  2. Michinori Ogura
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  3. Kohichi Takada
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  4. Masafumi Taniwaki
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  5. Fanghong Zhang
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  6. Taizo Fujita
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  7. Kiyoshi Ando
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Corresponding author

Correspondence to Kiyohiko Hatake.

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Conflict of interest

K Hatake has no conflicts of interest to declare. M. Taniwaki has received research funding from Chugai Pharmaceutical Co., Ltd. M. Ogura has received honoraria from Takeda Pharmaceuticals, Janssen Pharmaceuticals K.K and AstraZeneca K.K., and research funding from Eisai Co., Ltd., Takeda Pharmaceuticals, SymBio Pharmaceuticals, Janssen Pharmaceuticals K.K, and Chugai Pharmaceuticals Co., Ltd. K. Takada has no conflicts of interest to declare. K. Ando has received research funding from Renascience Co., Ltd. and Alexion Pharmaceuticals Inc., as well as subsidies or donations from Bristol-Myers Squibb, Kyowa Kirin, Mochida Pharmaceutical Co., Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd, Chugai Pharmaceutical Co., Ltd., and Eisai Co., Ltd.

Additional information

This trial is registered with ClinicalTrials.gov (NCT01563055).

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Hatake, K., Ogura, M., Takada, K. et al. Ofatumumab combined with chlorambucil for previously untreated chronic lymphocytic leukemia: a phase I/II, open-label study in Japan. Int J Hematol 106, 240–247 (2017). https://doi.org/10.1007/s12185-017-2233-1

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  • DOI: https://doi.org/10.1007/s12185-017-2233-1

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