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Pharmacogenomics Validation for Imatinib in Chronic Myeloid Leukemia (VATIC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dae-Young Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01437202
First received: September 19, 2011
Last updated: January 3, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Retrospective Study to Validate Pharmacogenetics Model for Imatinib Metabolism in Patients With Chronic Myeloid Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Median time to CCyR (complete cytogenetic response) [ Designated as safety issue: No ]
    Difference of median time to CCyR between cohorts according to the risk stratification by gene analysis


Secondary Outcome Measures:
  • Variance of Genotypes from CML patients with Korean ethnicity [ Designated as safety issue: No ]
  • Median time to MCyR (Major cytogenetic responses) [ Designated as safety issue: No ]
    Difference of median time to MCyR between cohorts according to the risk stratification by gene analysis


Biospecimen Retention:   Samples With DNA

whole blood 4cc


Enrollment: 100
Study Start Date: September 2011
Study Completion Date: October 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01437202

Locations
Canada
Princess Margaret Hospital, University of Toronto
Toronto, Canada
Korea, Republic of
Asan Medical Center, University of Ulsan College of Medicine
Seoul, Korea, Republic of
Samsung Medical Center, Sungkyunkwan University School of Medicine
Seoul, Korea, Republic of
Sponsors and Collaborators
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
  More Information

Publications:

Responsible Party: Dae-Young Kim, Assistant Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01437202     History of Changes
Other Study ID Numbers: AMC-H-64
Study First Received: September 19, 2011
Last Updated: January 3, 2013
Health Authority: Korea: Institutional Review Board

Keywords provided by Asan Medical Center:
imatinib
drug resistance
pharmacogenetics

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
 Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013