Pharmacogenomics Validation for Imatinib in Chronic Myeloid Leukemia (VATIC)

July 8, 2014 updated by: Dae-Young Kim, Asan Medical Center

Retrospective Study to Validate Pharmacogenetics Model for Imatinib Metabolism in Patients With Chronic Myeloid Leukemia

This is a multicenter, retrospective, observational study to validate a pharmacogenetics model for imatinib metabolism and resistance in patients with chronic myeloid leukemia among patients in different independent cohort.

Study Overview

Status

Completed

Conditions

Detailed Description

  1. The activity of Imatinib(IM) is mediated by blocking the activity of BCR/ABL tyrosine kinase in CML cells. However, some of the patients failed to achieve optimal response, and a substantial proportion of patients develop resistance to IM.
  2. IM is a substrate for the adenosine triphosphate binding cassette (ABC) transporters, ABCB1 and ABCG2, while the active uptake of IM into cells is mediated by the human organic cationic transporter-1 (hOCT1). Also, IM is metabolized through first pass drug metabolism by the cytochrome P450 - CYP3A4 and CYP3A5. In addition, it is delivered in a bound form with a plasma protein referred to α1-acid glycoprotein (AGP).
  3. Accordingly, the intracellular or systemic level of imatinib should be influenced by these factors such as ABCB1, ABCG2, hOCT1, CYP3A4, CYP3A5 or AGP genes. Inter-individual variability of 5 candidate genes associated with drug transport/metabolism (i.e. ABCB1, ABCG2, hOCT1, CYP3A4/3A5 and AGP) could affect the expression of corresponding proteins, thus influencing the treatment outcomes of imatinib therapy.
  4. In the investigators' previous study, the investigators reported the cumulative incidences of MCyR and CCyR was significantly affected by the predictive model using 2 genotypes and disease stage. These predictive models for CCyR/MMoR or LOR/treatment failure seemed to work well. However, external validation of these predictive models is warranted especially using ethnically different independent cohort.

Study Type

Observational

Enrollment (Actual)

100

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

  • Canada
      • Toronto, Canada
        • Princess Margaret Hospital, University of Toronto
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Samsung Medical Center, Sungkyunkwan University School of Medicine
      • Seoul, Korea, Republic of
        • Asan Medical Center, University of Ulsan College of Medicine

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients who were diagnosed as chronic myeloid leukemia, treated with imatinib more than 3 months, at Asan Medical Center, Seoul, Korea.

Description

Inclusion Criteria:

  • Chronic myeloid leukemia of any stage including chronic phase, accelerated or blastic phase.
  • Age>18 years
  • Complete set of clinical data available for review (demographic data, stage, treatment history, cytogenetic reports, and latest BCR/ABL RQ-PCR results)
  • Treated with imatinib mesylate at least 3 months

Exclusion Criteria:

  • Treated with imatinib mesylate less than 3 months
  • Not agree with the intention of this study

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
high risk group
Identified by the predictive model using 2 genotypes and disease stage
intermediate risk group
Identified by the predictive model using 2 genotypes and disease stage
Low risk group
Identified by the predictive model using 2 genotypes and disease stage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Median time to CCyR (complete cytogenetic response)
Difference of median time to CCyR between cohorts according to the risk stratification by gene analysis

Secondary Outcome Measures

Outcome Measure
Measure Description
Variance of Genotypes from CML patients with Korean ethnicity
Median time to MCyR (Major cytogenetic responses)
Difference of median time to MCyR between cohorts according to the risk stratification by gene analysis

Collaborators and Investigators

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

Sponsor

Asan Medical Center

Investigators

  • Study Chair: Jong Won Kim, MD, PhD, Samsung Medical Center, Sungjyunkwan University School of Medicine, Seoul, Korea
  • Principal Investigator: Dae-Young Kim, MD, Asan Medical Center, University of Ulsan College of Medicine, SEOUL, KOREA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

September 1, 2011

Primary Completion (ACTUAL)

September 1, 2012

Study Completion (ACTUAL)

October 1, 2012

Study Registration Dates

First Submitted

September 19, 2011

First Submitted That Met QC Criteria

September 19, 2011

First Posted (ESTIMATE)

September 20, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

July 9, 2014

Last Update Submitted That Met QC Criteria

July 8, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMC-H-64

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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