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.
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 Cmax 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.
Kobayashi
Yukio
Y
Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. ykkobaya@ncc.go.jp.
Tobinai
Kensei
K
Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Takeshita
Akihiro
A
The Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Naito
Kensuke
K
The Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Hamamatsu Medical Center, Hamamatsu, Japan.
Asai
Osamu
O
Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan.
Dobashi
Nobuaki
N
Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan.
Furusawa
Shinpei
S
Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan.
Saito
Kenji
K
Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan.|Saito Clinic, Tochigi, Japan.
Mitani
Kinuko
K
Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan.
Morishima
Yasuo
Y
Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan.
Ogura
Michinori
M
Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan.|Nagoya Daini Red Cross Hospital, Nagoya, Japan.
Yoshiba
Fumiaki
F
Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan.
Hotta
Tomomitsu
T
Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan.|National Nagoya Hospital, Nagoya, Japan.
Bessho
Masami
M
Department of Hematology, Saitama Medical University, School of Medicine, Saitama, Japan.
Matsuda
Shin
S
Center for Hematopoietic Disorders, Ohta Nishinouchi Hospital, Koriyama, Japan.
Takeuchi
Jin
J
Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.
Miyawaki
Shuichi
S
Leukemia Treatment Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
Naoe
Tomoki
T
Department of Hematology and Oncology, Nagoya University School of Medicine, Nagoya, Japan.
Usui
Noriko
N
Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan.
Ohno
Ryuzo
R
Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan.|Aichi Shukutoku University, Nagoya, Japan.
D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007564:Japan; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab