Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia

Children's Oncology Group

Status: Completed

Conditions: Leukemia

Treatments: Other: pharmacological study; Other: laboratory biomarker analysis; Genetic: microarray analysis; Genetic: gene expression analysis; Genetic: protein expression analysis; Genetic: western blotting; Genetic: reverse transcriptase-polymerase chain reaction

Study type: Observational

Funder types: NETWORK; NIH

Identifiers

NCT01150656

COG-AAML10B17 (Other Identifier)

AAML10B17 (Other Identifier)

NCI-2011-02239 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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 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.

Enrollment: 50 estimated patients

Sex: All

Ages: Under 2 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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