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Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia

2014-07-24 14:00:53 | BioPortfolio

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)

View Results

Links

Published on BioPortfolio: 2014-07-24T14:00:53-0400

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