Pharmacogenomics Validation for Imatinib in Chronic Myeloid Leukemia
NCT ID: NCT01437202
Last Updated: 2014-07-09
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
100 participants
OBSERVATIONAL
2011-09-30
2012-10-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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COHORT
RETROSPECTIVE
Study Groups
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high risk group
Identified by the predictive model using 2 genotypes and disease stage
No interventions assigned to this group
intermediate risk group
Identified by the predictive model using 2 genotypes and disease stage
No interventions assigned to this group
Low risk group
Identified by the predictive model using 2 genotypes and disease stage
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* 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
* Not agree with the intention of this study
18 Years
ALL
No
Sponsors
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Asan Medical Center
OTHER
Responsible Party
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Dae-Young Kim
Assistant Professor
Principal Investigators
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Jong Won Kim, MD, PhD
Role: STUDY_CHAIR
Samsung Medical Center, Sungjyunkwan University School of Medicine, Seoul, Korea
Dae-Young Kim, MD
Role: PRINCIPAL_INVESTIGATOR
Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Locations
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Princess Margaret Hospital, University of Toronto
Toronto, , Canada
Asan Medical Center, University of Ulsan College of Medicine
Seoul, , South Korea
Samsung Medical Center, Sungkyunkwan University School of Medicine
Seoul, , South Korea
Countries
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References
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Kantarjian HM, Cortes JE, O'Brien S, Luthra R, Giles F, Verstovsek S, Faderl S, Thomas D, Garcia-Manero G, Rios MB, Shan J, Jones D, Talpaz M. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004 Oct 1;104(7):1979-88. doi: 10.1182/blood-2004-02-0711. Epub 2004 Jun 15.
Kantarjian HM, Talpaz M, Giles F, O'Brien S, Cortes J. New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann Intern Med. 2006 Dec 19;145(12):913-23. doi: 10.7326/0003-4819-145-12-200612190-00008.
Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001 Aug 3;293(5531):876-80. doi: 10.1126/science.1062538. Epub 2001 Jun 21.
Mahon FX, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, Goldman JM, Melo JV. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood. 2003 Mar 15;101(6):2368-73. doi: 10.1182/blood.V101.6.2368.
Awidi A, Salem II, Najib N, Mefleh R, Tarawneh B. Determination of imatinib plasma levels in patients with chronic myeloid leukemia by high performance liquid chromatography-ultraviolet detection and liquid chromatography-tandem mass spectrometry: methods' comparison. Leuk Res. 2010 Jun;34(6):714-7. doi: 10.1016/j.leukres.2009.08.005. Epub 2009 Sep 9.
Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, Prenen H, de Jong FA, Baker SD, Bates SE, Figg WD, Verweij J, Sparreboom A, Nooter K. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther. 2006 Aug;80(2):192-201. doi: 10.1016/j.clpt.2006.05.003.
Kim DH, Sriharsha L, Xu W, Kamel-Reid S, Liu X, Siminovitch K, Messner HA, Lipton JH. Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res. 2009 Jul 15;15(14):4750-8. doi: 10.1158/1078-0432.CCR-09-0145. Epub 2009 Jul 7.
Other Identifiers
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AMC-H-64
Identifier Type: -
Identifier Source: org_study_id
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