Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia
Summary
RATIONALE: Studying the effects of obatoclax mesylate in cell samples from patients with cancer in the laboratory may help doctors learn more about the effects of obatoclax mesylate on cancer cells. It may also help doctors identify biomarkers related to cancer.
PURPOSE: This research study is studying obatoclax mesylate in samples from young patients with acute myeloid leukemia.
Description
OBJECTIVES:
- Determine comprehensive gene and protein expression profiles of in vitro sensitivity and resistance to obatoclax mesylate in multiple-lineage leukemia (MLL)-rearranged cell lines and primary infant acute myeloid leukemia (AML) samples.
- Define optimum in vitro combinations of obatoclax mesylate targeting pro-survival BCL-2 family proteins with cytotoxic drugs in MLL-rearranged leukemia cell lines and primary infant AML samples.
- Identify synergistic combinations based on a pharmacodynamic modeling and simulation construct.
- Determine whether combinations of obatoclax mesylate targeting pro-survival BCL-2 family proteins with cytotoxic drugs improves survival in a xenograft model of MLL-rearranged infant AML.
OUTLINE: This is a multicenter study.
Obatoclax activity is assessed via the MTT assay. A priori features of AML blasts relating to the apoptosis and ATG cell death pathways and their execution are characterized using microarray analysis and Q-RT PCR. Gene and protein expression is described and quantified using Q-RT PCR and western blot analysis at specific time points after obatoclax exposure to identify pharmacodynamic biomarkers of activity and characterize the cell death mechanism in MLL+ AML. The MTT assay is performed using obatoclax-cytotoxic chemotherapy combinations to determine synergy focusing on common cytotoxic drugs employed in AML treatment regimens.
Obatoclax efficacy is tested in a therapeutic NOG xenograft model of primary MLL+ infant AML.
Study Design
N/A
Conditions
Leukemia
Intervention
gene expression analysis, microarray analysis, protein expression analysis, reverse transcriptase-polymerase chain reaction, western blotting, laboratory biomarker analysis, pharmacological study
Status
Not yet recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01150656
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-07-24T14:00:53-0400
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MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Included are such techniques as IN SITU HYBRIDIZATION of chromosomes for CYTOGENETIC ANALYSIS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS of gene expression patterns in disease states; identification of pathogenic organisms by analysis of species specific DNA sequences; and detection of mutations with POLYMERASE CHAIN REACTION.
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Activation Analysis
A method of chemical analysis based on the detection of characteristic radionuclides following a nuclear bombardment. It is also known as radioactivity analysis. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Oligonucleotide Array Sequence Analysis
Hybridization of a nucleic acid sample to a very large set of oligonucleotide probes, which are attached to a solid support, to determine sequence or to detect variations in a gene sequence or expression or for gene mapping.
Network Meta-analysis
Meta-analysis of randomized trials in which estimates of comparative treatment effects are visualized and interpreted from a network of interventions that may or may not have been evaluated directly against each other. Common considerations in network meta-analysis include conceptual and statistical heterogeneity and incoherence.
