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

Int J Hematol. 2012 Oct;96(4):485-91. doi: 10.1007/s12185-012-1165-z. Epub 2012 Sep 6.

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 However, as GO was withdrawn from the US market in June 2010, based on a randomized study in newly diagnosed AML, we decided not to proceed to the level 3 (5 mg/m²) in order to avoid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

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aminoglycosides / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytarabine / administration & dosage
  • Cytarabine / analogs & derivatives
  • Daunorubicin / administration & dosage
  • Female
  • Gemtuzumab
  • Humans
  • Japan
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Neoplasm Staging
  • Recurrence
  • Treatment Outcome

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Cytarabine
  • Gemtuzumab
  • enocitabine
  • Daunorubicin