Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia
This study is to find out distribution of genetic polymorphisms and genes related to the chemotherapeutic drugs of ALL.
Acute Lymphoblastic Leukemia
|Study Design:||Time Perspective: Retrospective|
|Official Title:||Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia|
- To find out distribution of genetic polymorphisms genes related to the pharmacodynamics of the ALL therapy [ Time Frame: up to 3 years from diagnosis ] [ Designated as safety issue: No ]
- The distribution of each genetic polymorphism is descriped.
- The differences in genetic polymorphism between risk groups (high vs. standard) are analyzed using the chi-square test or Fisher's exact test.
- To see the ethnic difference of genetic polymorphisms related to the chemotehrapeutic drugs of ALL [ Time Frame: whenever after diagnosis and genetic analysis (no time frame needed) ] [ Designated as safety issue: No ]• The differences in genetic polymorphism between other populations (Korean vs. Western or Japanese) are analyzed using the chi-square test or Fisher's exact test.
- To find out relation of genetic polymorphisms and clinical outcome (relapse or survival) [ Time Frame: up to 3 years from diagnosis ] [ Designated as safety issue: No ]- Event-free and overall survival are estimated using Kaplan-Meier analysis, and the survival differences according to different genetic polymorphisms and prognostic variables are analyzed by log-rank test.
- To find out risk factors of relapse and death [ Time Frame: up to 3 years from diagnosis ] [ Designated as safety issue: No ]- Multivariate analysis is conducted with Cox proportional hazards regression model to analyze predictive factors. For the multivariate analysis, all significant univariate variables are entered in a stepwise, forward-selection protocol.
Biospecimen Retention: Samples With DNA
Candidate genes exhibit polymorphisms and encodes proteins that are involved in the pharmacokinetics and pharmacodynamics of antileukemic agents
- Priority was given to polymorphism that were demonstrated to be associated with phenotypes in both clinical and preclinical studies.
- Candidate genes : CYP3A4*1B, CYPA5*3, GSTM1 deletion, GSTP1 313, GSTT1 deletion, MDR exon 21, MDR exon 26, MTHFR 677, MTHFR 1298, NR3C1 1088, RFC 80, TPMT-1 238, TPMT-1 460, TPMT-1 719, VDR intron 8, VDR FokI, ITPA
- Blood sample at complete remission→DNA extraction
- Total-Plex (multiplex) PCR amplification
- Luminex system analysis
|Study Start Date:||June 2006|
|Study Completion Date:||May 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
|Pharmacogenetic analysis, ALL|
Cure rate of pediatric ALL dramatically improved over 80%. Resistance to drug and hematologic relapse are remaining problem in ALL treatment. One of the explanations of drug resistance and toxicities is the pharmacogenetic effect. Germline polymorphisms in genes that code for proteins involved in the pharmacokinetics and pharmacodynamics of antileukemic agents are various, and inter-patient variability is the main factor for pharmacogenetic difference. Since multiple chemotherapeutic agents are involved in treating ALL, many genes related to the metabolic pathways of those drugs have an effect on the pharmacokinetics of patients with ALL. In Korea, pharmacogenetic study including multiple genetic loci for pediatric ALL has not been reported.In this study, the distribution of genetic polymorphisms and genes related to antileukemic drugs were analyzed, and their relations to the outcome of treatment and relapse rates were assessed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01556386
|Korea, Republic of|
|Seoul National University Hospital|
|Seoul, Chongno-gu, Korea, Republic of|
|Principal Investigator:||Hyoung Jin Kang, MD. PhD.||Seoul National University Hospital|