Genetic Predictive Model Based on Single Nucleotide Polymorphisms in the DNA Repair Pathway and Drug Metabolis/Transport Pharmacogenetics in the Prediction of Response and Treatment Outcomes in Acute Myeloid Leukemia

May 23, 2011 updated by: Samsung Medical Center

The main component in the treatment of acute myeloid leukemia (AML) is consist of anthracycline (such as daunorubicin or idarubicin) and cytarabine. Inter-individual variability of transport/metabolism of the chemotherapeutic agent and several genetic pathways involved in the drug action might be associated with different response following the treatment for AML usually consisted of chemotherapy and/or transplantation. One of potential pathways involved in the drug action is DNA repair pathway, accordingly single nucleotide polymorphisms (SNPs) in the DNA repair machinery pathway might be a predictive marker for therapy outcomes in AML.

Several genes were involved in the DNA repair machinery which are 1) Nonhomologous end joining (NHEJ) pathway involved in the G1/S phase, 2) Homologous recombinational repair (HRR) pathway involved in the S/G2 phase. XRCC4, LIG4, MRN and ATM are well known genes involved in the NHEJ pathway, while MRE11, RAD50, NBS1 (MRN), RAD51, XRCC2, XRCC3, RAD51B, RAD51C, RAD 51D, RAD52 or RAD54 are known to be associated with HRR pathway.

A study suggested that the SNPs in the DNA repair pathway was involved in the susceptibility of secondary AML developing after chemotherapy or autologous hematopoietic stem cell transplantation, thus these SNP markers could become a predictive marker for secondary AML. However, it has never been investigated for multiple candidate pathways simultaneously with relateively larger number of patients. Accordingly, the current study attempts to investigate the potential role of the genotype markers in multiple candidate pathways, esp. focused on the DNA repair machinery, with respect to response following chemotherapy or survival of AML patients.

Total of over 500 archived samples from the patients diagnosed as acute myeloid leukemia at the Samsung Medical Center, Seoul, Korea will be included, and genomic DNAs will be extracted and will be examined for their genotypes of the candidate SNPs involved in the DNA repair pathways. Then statistical analysis will be pursued for single marker analysis, haplotype analysis and for the construction of genetic risk model based on the multivariate analysis.

Study Overview

Status

Unknown

Conditions

Study Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
    • South Korea
      • Seoul, South Korea, Korea, Republic of, 135-710
        • Recruiting
        • Samsung Medical Center IRB
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Adult patients with acute myeloid leukemia receiving induction/consolidation combination chemotherapy at Samsung Medical Center from 1996 to 2005

Description

Inclusion Criteria:

  • patients with acute myeloid leukemia
  • 15 years or older
  • patients treated with induction/consolidation chemotherapy
  • patients with available bone marrow sample

Exclusion Criteria:

  • acute biphenotypic leukemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Acute myeloid leukemia

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Investigators

  • Principal Investigator: Dong Hwan Kim, M.D., Ph.D., Samsung Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Study Registration Dates

First Submitted

April 15, 2010

First Submitted That Met QC Criteria

April 15, 2010

First Posted (Estimate)

April 19, 2010

Study Record Updates

Last Update Posted (Estimate)

May 24, 2011

Last Update Submitted That Met QC Criteria

May 23, 2011

Last Verified

May 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-08-094

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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