OBJECTIVES:
* Determine the safety and maximum tolerated dose of gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes.
* Determine the efficacy of this regimen in these patients.
* Correlate the likelihood of leukemic blast cells to undergo apoptosis in vitro with the efficacy of this regimen in these patients.
* Correlate drug resistance as manifested by dye efflux or multiple drug resistance-1 expression by leukemic blast cells with the efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation, multicenter study of gemtuzumab ozogamicin. Patients are assigned by cohort to 1 of 2 treatment regimens.
* Regimen A: Patients receive cytarabine IV over 2 hours every 12 hours on days 1-4, mitoxantrone IV over 1 hour on days 3-6, and gemtuzumab ozogamicin IV over 2 hours on day 7.
* Regimen B: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, asparaginase intramuscularly on days 2 and 9, and gemtuzumab ozogamicin IV over 2 hours on day 3.
Cohorts of 3-6 patients receive de-escalating doses of gemtuzumab ozogamicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose below that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed monthly for 6 months, every 2 months for 6 months, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 1.5 years.
