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.
Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. ykkobaya@ncc.go.jp.
Yukio
Y
Kobayashi
Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Kensei
K
Tobinai
The Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Akihiro
A
Takeshita
The Third Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.|Hamamatsu Medical Center, Hamamatsu, Japan.
Kensuke
K
Naito
Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan.
Osamu
O
Asai
Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan.
Nobuaki
N
Dobashi
Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan.
Shinpei
S
Furusawa
Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan.|Saito Clinic, Tochigi, Japan.
Kenji
K
Saito
Department of Hematology, Dokkyo Medical School of Medicine, Tochigi, Japan.
Kinuko
K
Mitani
Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan.
Yasuo
Y
Morishima
Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan.|Nagoya Daini Red Cross Hospital, Nagoya, Japan.
Michinori
M
Ogura
Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan.
Fumiaki
F
Yoshiba
Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan.|National Nagoya Hospital, Nagoya, Japan.
Tomomitsu
T
Hotta
Department of Hematology, Saitama Medical University, School of Medicine, Saitama, Japan.
Masami
M
Bessho
Center for Hematopoietic Disorders, Ohta Nishinouchi Hospital, Koriyama, Japan.
Shin
S
Matsuda
Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.
Jin
J
Takeuchi
Leukemia Treatment Center, Saiseikai Maebashi Hospital, Maebashi, Japan.
Shuichi
S
Miyawaki
Department of Hematology and Oncology, Nagoya University School of Medicine, Nagoya, Japan.
Tomoki
T
Naoe
Department of Clinical Oncology and Hematology, School of Medicine, The Jikei University, Tokyo, Japan.
Noriko
N
Usui
Hematology and Cell Therapy Division, Aichi Cancer Center Hospital, Nagoya, Japan.|Aichi Shukutoku University, Nagoya, Japan.
Ryuzo
R
Ohno
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