Obatoclax Mesylate in Samples From Young Patients With Acute Myeloid Leukemia
SCOR in Targeted Therapies for Infant Leukemias Project 2: Targeting Apoptosis in Leukemia in Infants
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.
Studieoversigt
Status
Betingelser
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Forventet)
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
DISEASE CHARACTERISTICS:
- Diagnosis of acute myeloid leukemia (AML)
- Cryopreserved samples from infants with AML available
PATIENT CHARACTERISTICS:
- Not specified
PRIOR CONCURRENT THERAPY:
- Not specified
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
|---|
|
Obatoclax mesylate activity
|
|
Optimum in vitro combinations of obatoclax mesylate
|
|
Pharmacodynamic (PD) biomarkers of activity
|
|
Cell death mechanism in multiple-lineage leukemia (MLL) acute myeloid leukemia (AML)
|
|
Disease progression in a xenograft model of MLL-rearranged infant AML
|
Sekundære resultatmål
Resultatmål |
|---|
|
Physical assessment (in xenograft model)
|
|
Peripheral blast count reduction
|
|
Apoptosis and/or ATG induction
|
|
Modulation of relevant PD biomarkers
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Carolyn A. Felix, MD, Children's Hospital of Philadelphia
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- AAML10B17 (Anden identifikator: Children's Oncology Group)
- COG-AAML10B17 (Anden identifikator: Children's Oncology Group)
- NCI-2011-02239 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med genekspressionsanalyse
-
Centre Médico-Chirurgical de Réadaptation des Massues...RekrutteringIdiopatisk skolioseFrankrig
-
Pusan National University HospitalAfsluttet
-
Liao Jian AnRekrutteringHoved- og halskræftTaiwan
-
Nantes University HospitalIkke rekrutterer endnuRettsmedicinsk Tandlægevidenskab | Bidanalyse
-
Fondation LenvalTrukket tilbage
-
Daniel MarotiWayne State UniversityRekrutteringSomatisk symptomlidelse | Funktionel somatisk lidelse | Funktionelle somatiske syndromerSverige
-
Kessler FoundationIkke rekrutterer endnuADHD | Ordblindhed | Indlæringsvanskeligheder
-
Kessler FoundationRekrutteringAutismespektrumforstyrrelseForenede Stater
-
IRCCS Eugenio MedeaRekrutteringCerebral Parese | Erhvervet hjerneskadeItalien
-
Fondazione Policlinico Universitario Agostino Gemelli...Ikke rekrutterer endnu