Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00898456
• Other study ID #: CALGB-20501
• Secondary ID: CALGB-20501U10CA
• Status: Active, not recruiting
• Start date: October 2006

Study information

• Verified date: August 2023
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. primary completion date: January 2100
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Genetic:
• gene expression analysis

• molecular genetic technique

• polymorphism analysis

• protein expression analysis

Other:
• diagnostic laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms on treatment outcome		Baseline
Secondary	Association of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes with Pgp, MRP-1, and BCRP function and expression in pre-treatment blasts		Baseline
Secondary	Effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp, MRP-1, and BCRP function		Baseline
Secondary	Association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity		Baseline