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.

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 However, as GO was withdrawn from the US market in June 2010, based on a randomized study in newly diagnosed AML, we decided not to proceed to the level 3 (5 mg/m²) in order to avoid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.