This phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
OBJECTIVES: 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 retinoids. 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 toxicity. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, Canada
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time frame: Up to day 28
Minimal effective dose of decitabine that will lead to demethylation of deoxyribonucleic acid (DNA) with tolerable toxicity as assessed by RXR gene
Time frame: Up to day 28
Proportion of patients with in-vitro retinoid response
Time frame: Up to 8 years
Duration of clinical response
Time frame: Up to 8 years
Changes in gene expression, gene methylation and bone marrow aspirate sample measurements
The effect on gene expression due to pharmacological exposures (ie retinoic acid receptor \[RAR\] or retinoid X receptor \[RXR\]) will be assessed using chi-square tests.
Time frame: Up to day 5
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