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SCOR in Targeted Therapies for Infant Leukemias Project 2: Targeting Apoptosis in Leukemia in Infants


N/A
N/A
2 Years
Open (Enrolling)
Both
Leukemia

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Trial Information

SCOR in Targeted Therapies for Infant Leukemias Project 2: Targeting Apoptosis in Leukemia in Infants


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.

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

Type of Study:

Observational

Study Design:

N/A

Outcome Measure:

Obatoclax mesylate activity

Safety Issue:

No

Principal Investigator

Carolyn A. Felix, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Hospital of Philadelphia

Authority:

United States: Federal Government

Study ID:

CDR0000675718

NCT ID:

NCT01150656

Start Date:

June 2010

Completion Date:

Related Keywords:

  • Leukemia
  • childhood acute myeloid leukemia/other myeloid malignancies
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

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