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Phase I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study |
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| Authors: | Yukio Kobayashi Kensei Tobinai Akihiro Takeshita Kensuke Naito Osamu Asai Nobuaki Dobashi Shinpei Furusawa Kenji Saito Kinuko Mitani Yasuo Morishima Michinori Ogura Fumiaki Yoshiba Tomomitsu Hotta Masami Bessho Shin Matsuda Jin Takeuchi Shuichi Miyawaki Tomoki Naoe Noriko Usui Ryuzo Ohno |
| Affiliation: | 1. Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan 2. The Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan 12. Hamamatsu Medical Center, Hamamatsu, Japan 3. Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan 4. Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan 13. Saito Clinic, Tochigi, Japan 5. Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan 14. Nagoya Daini Red Cross Hospital, Nagoya, Japan 6. Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan 15. National Nagoya Hospital, Nagoya, Japan 7. Department of Hematology, Saitama Medical University, School of Medicine, Saitama, Japan 8. Center for Hematopoietic Disorders, Ohta Nishinouchi Hospital, Koriyama, Japan 9. Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan 10. Leukemia Treatment Center, Saiseikai Maebashi Hospital, Maebashi, Japan 11. Department of Hematology and Oncology, Nagoya University School of Medicine, Nagoya, Japan 16. Aichi Shukutoku University, Nagoya, Japan |
| Abstract: | The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of gemtuzumab ozogamicin (GO) in patients with relapsed and/or refractory CD33-positive acute myeloid leukemia (AML). Patients received 2-h infusions of GO twice with an interval of approximately 14 days. Tolerability was assessed using the National Cancer Institute Common Toxicity Criteria Version 2.0. Samples for pharmacokinetics were taken on day 1 and day 8 of the first treatment cycle. The dose was increased stepwise and, in each cohort, patients were treated at the same dose. Forty patients, median age 58 years (range 28–68) were treated; 20 and 20 patients were enrolled to the phase I and II parts, respectively. In the phase I part, dose-limiting toxicities (DLTs) were hepatotoxicities, and the recommended dose was established as 9 mg/m2 given as two intravenous infusions separated by approximately 14 days. The pharmacokinetic study revealed that C max and AUC were equivalent to those of non-Japanese patients. In the phase II part, complete remission was observed in 5 patients, and one patient had complete remission without platelet recovery. Four of these 6 in remission and one in the phase I are long-term survivors (alive for at least 44 months). GO is safe and effective as a single agent among Japanese CD33-positive AML patients. Remission lasted longer in a subset of patients than in non-Japanese patients in earlier studies. Further studies of this agent are warranted to establish standard therapy. S. Furusawa: deceased. |
| Keywords: | Gemtuzumab ozogamicin AML Pharmacokinetic study Phase I/II study |
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