Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia
- Conditions
- Leukemia
- Interventions
- Genetic: gene expression analysisGenetic: molecular genetic techniqueGenetic: polymorphism analysisGenetic: protein expression analysisOther: diagnostic laboratory biomarker analysis
- Registration Number
- NCT00898456
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This research trial studies multidrug resistance genes in patients with acute myeloid leukemia. Studying samples of bone marrow or blood from patients with cancer in the laboratory may help doctors learn more about changes that may occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer. It may also help doctors learn more about drug resistance and how patients respond to treatment.
- Detailed Description
PRIMARY OBJECTIVES:
I. To investigate the association of common single nucleotide polymorphisms (SNPs) and haplotypes of the three multidrug resistance (MDR) genes with treatment outcome in the clinical studies.
II. To assess the effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms and haplotypes on treatment outcome in younger patients enrolled on Cancer and Leukemia Group B (CALGB) 9621 and 19808.
III. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on treatment outcome in older patients enrolled on CALGB 9720.
SECONDARY OBJECTIVES:
I. To test the hypothesis that ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes are associated with phosphoglycolate phosphatase (Pgp), multidrug resistance protein 1 (MRP-1), and ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group) (BCRP) function and expression in pre-treatment blasts from acute myeloid leukemia (AML) patients.
II. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on PGP, MRP-1, and BCRP function through CALGB 9760 in younger patients enrolled on CALGB 9621 and 19808.
III. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on PGP, MRP-1, and BCRP function through CALGB 9760 in older patients from CALGB 9720.
IV. To conduct an exploratory analysis of the association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity.
OUTLINE:
Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760.
PROJECTED ACCRUAL: Tissue samples from over 600 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 600
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Group 1 polymorphism analysis Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760. Group 1 protein expression analysis Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760. Group 1 gene expression analysis Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760. Group 1 molecular genetic technique Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760. Group 1 diagnostic laboratory biomarker analysis Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760.
- Primary Outcome Measures
Name Time Method Correlation of common single nucleotide polymorphisms (SNPs) and haplotypes of the 3 multidrug resistance genes (P-glycoprotein [Pgp], multidrug resistance-associated protein (MRP-1) and breast cancer resistance protein [BCRP]) with treatment outcome Baseline Effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms on treatment outcome Baseline
- Secondary Outcome Measures
Name Time Method Effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp, MRP-1, and BCRP function Baseline Association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity Baseline Association of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes with Pgp, MRP-1, and BCRP function and expression in pre-treatment blasts Baseline
Trial Locations
- Locations (1)
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States