Genome-wide Single Nucleotide Polymorphism (SNP) Array-based Approach to Predict Chemoresponse and Survival in Patients With Acute Lymphoblastic Leukemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Samsung Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01079507
First received: March 1, 2010
Last updated: March 2, 2010
Last verified: March 2010
  Purpose

Acute lymphoblastic leukemia (ALL) is not a single disease, but a composite of heterogeneous subgroup. Accordingly, more sophisticated classification in ALL is essential to achieve further improvement of treatment outcomes. However, only a few genetic markers are revealed to have significant prognostic implications in ALL patients. The current study is designed to stratify the ALL patients according to their prognosis and to predict their outcomes by a pharmacogenetic approach. A predictive model will be generated from 130 genotypes in adult ALL patients diagnosed at the Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine, Seoul,Korea between 1994 and 2008. The validation of the predictive model will be performed using an independent external cohort of ALL patients.

  1. Definition of the cohort: two hundred ALL patients from the SMC as a test set, another 100 patients from the SMC as a first validation set, and another 150 independent external patients as second external validation set. DNAs will be extracted and stored from patients' samples collected at the time of diagnosis.
  2. In the test set, genotypes will be determined using a MALDI-TOF based platform (Sequenom, San Diego, CA, USA) for 130 SNPs of the candidate genes involved in DNA repair pathway, drug metabolism/transport pathway and folate metabolism pathway.
  3. Bioinformatic analyses will be performed to identify around 13 genotypes (10%) having strongest predictive significance out of these 130 SNPs in terms of their treatment outcomes, drug toxicity and prognosis in the test set.
  4. These 13 genotypes will be validated in the first cohort of 100 ALL patients using a multivariate Cox's proportional hazard model.
  5. The predictive model will be built up based on Cox's proportional hazard model derived from 13 candidate genotypes and clinical risk factors.
  6. The predictive model based on pharmacogenetic information will be validated again in the second, independent external cohort of 150 ALL patients.

Definite prognostic value was not established for genetic or molecular markers in acute lymphoblastic leukemia (ALL) except BCR/ABL fusion gene. The current study attempts to build up a predictive model based on single nucleotide polymorphisms (SNPs) with pharmacogenetic approach using 130 genotypes in the multiple candidate pathways such as DNA repair pathway, drug metabolism / transport pathway and folate metabolism pathway. The predictive model based on SNPs will be generated and validated with respect to treatment outcomes, drug toxicity and prognosis in adult ALL patients.

The present study will demonstrate that: 1) Pharmacogenetic information derived from SNPs involved in the DNA repair pathway, drug metabolism/transport pathway and folate metabolism pathway, is helpful to predict the treatment outcomes, drug toxicity and prognosis in ALL patients; 2) Predictive model derived from pharmacogenetic information will be effective and reasonable approach to stratify ALL patients according to their clinical outcomes; 3) The SNP-based predictive model could be reasonably applied to the treatment of ALL patients, thus becoming a basis for further improvement of treatment outcome; 4) Finally, this project will enhance and facilitate the pharmacogenetic research in the hematology area, thus make the team to lead the pharmacogenetic research in the world.


Condition
Acute Lymphoblastic Leukemia

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Genome-wide Single Nucleotide Polymorphism (SNP) Array-based Approach to Predict Chemoresponse and Survival in Patients With Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • response rate [ Time Frame: within 1 month after enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival and progression-free survival [ Time Frame: within 1 month after enrollment ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Stored bone marrow specimens of patients with acute lymphoblastic leukemia


Estimated Enrollment: 200
Study Start Date: February 2010
Groups/Cohorts
adult acute lymphoblastic leukemia
Patients were diagnosed as adult acute lymphoblastic leukemia.

  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 were diagnosed as adult acute lymphoblastic leukemia at Samsung Medical Center(Sungkyunkwan University School of Medicine, Seoul, South Korea) between 1994 and 2008.

Criteria

Inclusion Criteria:

  • patients with core binding factor positive acute myeloid leukemia
  • 18 years or older
  • patients were treated with standard chemotherapy
  • patients with available medical record and stored bone marrow specimen at time of diagnosis

Exclusion Criteria:

  • no definitive criteria
  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: NCT01079507

Contacts
Contact: Dong Hwan Kim, M.D.,Ph.D. +82-2-3410-1768 dr.dennis.kim@samsung.com

Locations
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Dong Hwan Kim, M.D., Ph. D.    +82-2-3410-1768    dr.dennis.kim@samsung.com   
Principal Investigator: Dong Hwan Kim, M.D.,Ph.D.         
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: Dong Hwan Kim, M.D.,Ph.D. Division of Hematology and Oncology/Samsung Medical Center
  More Information

No publications provided

Responsible Party: Dong Hwan (Dennis) Kim/Assistant professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01079507     History of Changes
Other Study ID Numbers: 2009-06-060
Study First Received: March 1, 2010
Last Updated: March 2, 2010
Health Authority: South Korea: Institutional Review Board

Keywords provided by Samsung Medical Center:
single nucleotide polymorphism
adult acute lymphoblastic leukemia

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 28, 2014