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Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia

Multidrug Resistance Protein Gene Polymorphisms in Acute Myeloid Leukemia. A CALGB Leukemia Tissue Bank Project

Status
Active, not recruiting
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT00898456
Enrollment
600
Registered
2009-05-12
Start date
2006-10-31
Completion date
Unknown
Last updated
2023-08-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia

Keywords

adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute basophilic leukemia, adult acute eosinophilic leukemia

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.

Interventions

GENETICgene expression analysis
GENETICpolymorphism analysis
GENETICprotein expression analysis
OTHERdiagnostic laboratory biomarker analysis

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Alliance for Clinical Trials in Oncology
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
RETROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No

Inclusion criteria

DISEASE CHARACTERISTICS: * Diagnosis of acute myeloid leukemia * Treated on protocols CALGB-9621, CALGB-9720, or CALGB-19808 * Registered on the mandatory companion Leukemia Tissue Bank Protocol CALGB-9665 * Registration on another companion trial, CALGB-9760, (Multidrug Resistance Studies in Acute Leukemia) allowed PATIENT CHARACTERISTICS: * Not specified PRIOR CONCURRENT THERAPY: * See Disease Characteristics

Design outcomes

Primary

MeasureTime frame
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 outcomeBaseline
Effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms on treatment outcomeBaseline

Secondary

MeasureTime frame
Effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp, MRP-1, and BCRP functionBaseline
Association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicityBaseline
Association of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes with Pgp, MRP-1, and BCRP function and expression in pre-treatment blastsBaseline

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026