Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00898456
First received: May 9, 2009
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention
Leukemia
Genetic: gene expression analysis
Genetic: molecular genetic technique
Genetic: polymorphism analysis
Genetic: protein expression analysis
Other: diagnostic laboratory biomarker analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Multidrug Resistance Protein Gene Polymorphisms in Acute Myeloid Leukemia. A CALGB Leukemia Tissue Bank Project

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms on treatment outcome [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Association of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes with Pgp, MRP-1, and BCRP function and expression in pre-treatment blasts [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on Pgp, MRP-1, and BCRP function [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: October 2006
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Group 1
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.
Genetic: gene expression analysis Genetic: molecular genetic technique Genetic: polymorphism analysis Genetic: protein expression analysis Other: diagnostic laboratory biomarker analysis

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with acute myeloid leukemia enrolled on CALGB-9621, CALGB-9720, or CALGB-19808

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
  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: NCT00898456

Locations
United States, Indiana
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46845
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Maria R. Baer, MD University of Maryland Greenebaum Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00898456     History of Changes
Other Study ID Numbers: CALGB-20501, CALGB-20501, U10CA031946, U10CA180821, CDR0000514506
Study First Received: May 9, 2009
Last Updated: July 23, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
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

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

ClinicalTrials.gov processed this record on July 30, 2015