Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hyo Seop Ahn, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01556386
First received: March 8, 2012
Last updated: July 11, 2014
Last verified: December 2013
  Purpose

This study is to find out distribution of genetic polymorphisms and genes related to the chemotherapeutic drugs of ALL.


Condition
Acute Lymphoblastic Leukemia

Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
  1. 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
  2. Blood sample at complete remission→DNA extraction
  3. Total-Plex (multiplex) PCR amplification
  4. Luminex system analysis

Estimated Enrollment: 200
Study Start Date: June 2006
Study Completion Date: May 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pharmacogenetic analysis, ALL

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

All the patients with acute lymphoblastic leukemia who was diagnosed and treated in SNUCH.

Criteria

Inclusion Criteria:

  • Clinical diagnosis of acute lymphoblastic leukemia
  • In case of informed consent and assent

Exclusion Criteria:

  • Paients or parents refusal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556386

Locations
Korea, Republic of
Seoul National University Hospital
Seoul, Chongno-gu, Korea, Republic of
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Hyoung Jin Kang, MD. PhD. Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Hyo Seop Ahn, MD. Ph D., Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01556386     History of Changes
Other Study ID Numbers: SNUCH-1202
Study First Received: March 8, 2012
Last Updated: July 11, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:
acute lymphoblastic leukemia
single nucleotide polymorphism

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 23, 2014