title: Phase 1 trial of gemtuzumab ozogamicin in combination with enocitabine and daunorubicin for elderly patients with relapsed or refractory acute myeloid leukemia: Japan Adult Leukemia Study Group (JALSG)-GML208 study.
abstract: We conducted a phase 1 study of a combination of gemtuzumab ozogamicin (GO) plus conventional chemotherapy in elderly patients (≥ 65 years old) with relapsed or refractory CD33-positive acute myeloid leukemia (AML). Patients received a standard dose of enocitabine (200 mg/m² × 8 days) and daunorubicin (30 mg/m² × days 1-3) plus an escalating dose of GO (1.5-5 mg/m² on day 4). The dose escalation of GO was done according to a standard 3 + 3 design following a modified Fibonacci sequence. No dose-limiting toxicities were observed in three patients (median age, 71) at level 1 (1.5 mg/m²) or in three patients (median age, 73) at level 2 (3 mg/m²). Neither veno-occlusive diseases nor sinusoidal obstructive syndromes were noted at either level. However, as GO was withdrawn from the US market in June 2010, based on a randomized study in newly diagnosed AML, we decided not to proceed to the level 3 (5 mg/m²) in order to avoid possibly more severe adverse effects, and also because all six patients experienced grade 4 myelosuppression, with complete remission in three. This study showed that 3 mg/m² of GO in combination with enocitabine and daunorubicin may be a recommendable dose for a phase 2 study in Japanese elderly patients with CD33-positive AML. The study was registered at the University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ) as UMIN000002603.
authors.affiliation: Division of Hematology, First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. yito@tokyo-med.ac.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Wakita
authors.forename: Satoru
authors.initials: S
authors.lastname: Takada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mihara
authors.forename: Moritaka
authors.initials: M
authors.lastname: Gotoh
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007564:Japan; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab; C015019:enocitabine; D003630:Daunorubicin