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

18 Years
Not Enrolling
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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Trial Information

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

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.

Inclusion Criteria:

- Chronic myeloid leukemia of any stage including chronic phase, accelerated or blastic

- 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

Type of Study:


Study Design:

Observational Model: Cohort, Time Perspective: Retrospective

Outcome Measure:

Median time to CCyR (complete cytogenetic response)

Outcome Description:

Difference of median time to CCyR between cohorts according to the risk stratification by gene analysis

Safety Issue:


Principal Investigator

Jong Won Kim, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Samsung Medical Center, Sungjyunkwan University School of Medicine, Seoul, Korea


Korea: Institutional Review Board

Study ID:




Start Date:

September 2011

Completion Date:

October 2012

Related Keywords:

  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • imatinib
  • drug resistance
  • pharmacogenetics
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive