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)
Overview
- Phase
- Phase 1
- Intervention
- decitabine
- Conditions
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •One of the following diagnoses:
- •High-risk myelodysplastic syndromes (MDS)
- •Acute myeloid leukemia (AML)
- •De novo, secondary, or relapsed disease
- •Any number of prior regimens for primary or relapsed disease
- •Ineligible for or refuses aggressive management
- •Measurable disease, defined as:
- •More than 5% blasts in bone marrow of patients with MDS
- •More than 30% blasts in bone marrow of patients with AML
- •Involvement of cerebrospinal fluid allowed
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (decitabine)
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 MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Intervention: decitabine
Treatment (decitabine)
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 MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Intervention: laboratory biomarker analysis
Treatment (decitabine)
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 MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Intervention: pharmacological study
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Changes in gene expression, gene methylation and bone marrow aspirate sample measurements(Up to day 5)
- Minimal effective dose of decitabine that will lead to demethylation of deoxyribonucleic acid (DNA) with tolerable toxicity as assessed by RXR gene(Up to day 28)
- Proportion of patients with in-vitro retinoid response(Up to 8 years)
- Duration of clinical response(Up to 8 years)