Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia

NCT ID: NCT01150656

Last Updated: 2016-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-06-30

Brief Summary

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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.

Detailed Description

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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 mesylate activity is assessed via the MTT assay. A priori features of acute myeloid leukemia (AML) blasts relating to the apoptosis and ATG cell death pathways and their execution are characterized using microarray analysis and quantitative real-time (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 mesylate exposure to identify pharmacodynamic biomarkers of activity and characterize the cell death mechanism in multiple-lineage leukemia (MLL)+ AML. The MTT assay is performed using obatoclax mesylate-cytotoxic chemotherapy combinations to determine synergy focusing on common cytotoxic drugs employed in AML treatment regimens.

Obatoclax mesylate efficacy is tested in a therapeutic NOG xenograft model of primary MLL+ infant AML.

Conditions

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Leukemia

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Interventions

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gene expression analysis

Intervention Type GENETIC

microarray analysis

Intervention Type GENETIC

protein expression analysis

Intervention Type GENETIC

reverse transcriptase-polymerase chain reaction

Intervention Type GENETIC

western blotting

Intervention Type GENETIC

laboratory biomarker analysis

Intervention Type OTHER

pharmacological study

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Diagnosis of acute myeloid leukemia (AML)
* Cryopreserved samples from infants with AML available

PATIENT CHARACTERISTICS:

* Not specified

PRIOR CONCURRENT THERAPY:

* Not specified
Maximum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carolyn A. Felix, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Other Identifiers

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COG-AAML10B17

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2011-02239

Identifier Type: REGISTRY

Identifier Source: secondary_id

AAML10B17

Identifier Type: OTHER

Identifier Source: secondary_id

AAML10B17

Identifier Type: -

Identifier Source: org_study_id

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