Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01150656
First received: June 24, 2010
Last updated: February 4, 2011
Last verified: February 2011
  Purpose

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.


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

Study Type: Observational
Official Title: SCOR in Targeted Therapies for Infant Leukemias Project 2: Targeting Apoptosis in Leukemia in Infants

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Obatoclax mesylate activity [ Designated as safety issue: No ]
  • Optimum in vitro combinations of obatoclax mesylate [ Designated as safety issue: No ]
  • Pharmacodynamic (PD) biomarkers of activity [ Designated as safety issue: No ]
  • Cell death mechanism in multiple-lineage leukemia (MLL) acute myeloid leukemia (AML) [ Designated as safety issue: No ]
  • Disease progression in a xenograft model of MLL-rearranged infant AML [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Physical assessment (in xenograft model) [ Designated as safety issue: No ]
  • Peripheral blast count reduction [ Designated as safety issue: No ]
  • Apoptosis and/or ATG induction [ Designated as safety issue: No ]
  • Modulation of relevant PD biomarkers [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2010
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01150656

Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Carolyn A. Felix, MD Children's Hospital of Philadelphia
  More Information

Additional Information:
No publications provided

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT01150656     History of Changes
Other Study ID Numbers: CDR0000675718, COG-AAML10B17
Study First Received: June 24, 2010
Last Updated: February 4, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
childhood acute myeloid leukemia/other myeloid malignancies

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 23, 2014