Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia
Summary
This phase I trial is studying the side effects and best dose of bortezomib when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with decitabine may kill more cancer cells
Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of bortezomib (Velcade, PS-341) in combination with decitabine in patients with acute myeloid leukemia (AML) II. To define the specific toxicities and the dose limiting toxicity (DLT) of decitabine plus bortezomib combination
SECONDARY OBJECTIVES:
I. To determine the overall response rate (ORR). II. To determine the rate of complete remission (CR) of decitabine plus bortezomib in AML III. To correlate the biological activity of decitabine as demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints and plasma pharmacokinetics of decitabine.
IV. To characterize the biological activity of bortezomib as a potential demethylating agent V. To correlate intracellular concentration of decitabine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response.
VI. To explore the biologic role of microRNAs in determining clinical response to the decitabine plus bortezomib combination and achievement of the other pharmacodynamic endpoints.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive decitabine intravenously (IV) over 1 hour on days 1-5 or 1-10 and bortezomib IV on days 5 and 8 or days 5, 8, 12, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose is determined, an additional 6 patients are treated at the recommended phase II dose.
After completion of study treatment, patients are followed for at least 30 days.
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Intervention
bortezomib, decitabine, pharmacological study, laboratory biomarker analysis, DNA methylation analysis, RNA analysis
Location
Ohio State University Medical Center
Columbus
Ohio
United States
43210
Status
Active, not recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00703300
- Information obtained from ClinicalTrials.gov on April 16, 2013
Medical and Biotech [MESH] Definitions
Matched-pair Analysis
A type of analysis in which subjects in a study group and a comparison group are made comparable with respect to extraneous factors by individually pairing study subjects with the comparison group subjects (e.g., age-matched controls).
Costs And Cost Analysis
Absolute, comparative, or differential costs pertaining to services, institutions, resources, etc., or the analysis and study of these costs.
Multivariate Analysis
A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.
Proportional Hazards Models
Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time.
Biotechnology
Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.
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