A Randomized Study Of The Safety And Efficacy Of Two Dose Schedules Of Gemcituzumab Ozogamicin In Patients With Intermediate-2 Or High-Risk Myelodysplastic Syndromes

OBJECTIVES: I. Determine the total survival of patients with intermediate-2 or high-risk myelodysplastic syndrome treated with gemtuzumab ozogamicin. II. Assess the quality of life of patients treated with this drug. III. Compare two different dose schedules of this drug in these patients. IV. Determine the safety of this drug in these patients. V. Determine the number of patients treated with this drug that achieve complete remission, partial remission, stable disease, major and minor hematologic improvements, or major and minor cytogenetic responses. VI. Determine the progression-free survival, relapse-free survival, and time to progression to acute myeloid leukemia in patients treated with this drug. VII. Determine the number of transfusions, number of days on IV antibiotics, and the number of days hospitalized in patients treated with this drug. VIII. Determine the possible predictors of response in patients treated with this drug, including age, karyotype, and multi-drug resistance efflux. IX. Determine the pharmacokinetics of this drug in these patients. X. Correlate the results of pharmacogenomic studies to gene activation and response to therapy in patients treated with this drug.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to age (60 and under vs over 60) and IPSS score (1.5-2.0 vs 2.5 and greater). Patients are randomized to one of two treatment arms. Arm I: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1. Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. After completion of induction therapy, patients in both arms with stable or responding disease may receive post-remission therapy comprising up to 3 additional doses of gemtuzumab ozogamicin approximately 28-42 days apart. Quality of life is assessed at baseline, on day 29 for arm I, on day 43 for arm II, on day 127 for patients that receive additional doses of study drug, and at 8 months for all patients. Patients who do not respond to induction therapy are followed monthly for 8 months and then every 3 months thereafter. Patients who receive post-remission therapy are followed every 3 months.

PROJECTED ACCRUAL: Approximately 128 patients (64 per treatment arm) will be accrued for this study within 12 months.