Phase I Study Of 5-aza-2'-Deoxycytidine (Decitabine) As A Biologic Modifier Of Retinoid Responsive Genes In Patients With High-Risk Myelodysplastic Syndromes And Acute Myelogenous Leukemia (De-novo, Relapsed or Secondary)
I. Determine the maximum tolerated dose of decitabine in patients with high-risk
myelodysplastic syndromes or acute myeloid leukemia.
II. Determine the minimum effective dose of this drug that produces demethylation of DNA
with tolerable toxicity in these patients.
III. Determine the minimum effective dose of this drug that augments in vitro responses to
IV. Determine the pharmacokinetics of this drug in these patients. V. Determine the clinical
response rate of patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days
1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable
Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 18 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to day 28
Princess Margaret Hospital Phase 2 Consortium
United States: Food and Drug Administration