Genome-wide Single Nucleotide Polymorphism (SNP) Array-based Approach to Predict Chemoresponse and Survival in Patients With Acute Lymphoblastic Leukemia
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01079507 |
|
Recruitment Status : Unknown
Verified March 2010 by Samsung Medical Center.
Recruitment status was: Recruiting
First Posted : March 3, 2010
Last Update Posted : March 3, 2010
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
- 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.
- 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.
- 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.
- These 13 genotypes will be validated in the first cohort of 100 ALL patients using a multivariate Cox's proportional hazard model.
- The predictive model will be built up based on Cox's proportional hazard model derived from 13 candidate genotypes and clinical risk factors.
- 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 or disease |
|---|
| Acute Lymphoblastic Leukemia |
| Study Type : | Observational |
| Estimated Enrollment : | 200 participants |
| 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 |
| Study Start Date : | February 2010 |
| Group/Cohort |
|---|
|
adult acute lymphoblastic leukemia
Patients were diagnosed as adult acute lymphoblastic leukemia.
|
- response rate [ Time Frame: within 1 month after enrollment ]
- overall survival and progression-free survival [ Time Frame: within 1 month after enrollment ]
Biospecimen Retention: Samples With DNA
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01079507
| Contact: Dong Hwan Kim, M.D.,Ph.D. | +82-2-3410-1768 | dr.dennis.kim@samsung.com |
| 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. | |
| Principal Investigator: | Dong Hwan Kim, M.D.,Ph.D. | Division of Hematology and Oncology/Samsung Medical Center |
| 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 |
| First Posted: | March 3, 2010 Key Record Dates |
| Last Update Posted: | March 3, 2010 |
| Last Verified: | March 2010 |
Keywords provided by Samsung Medical Center:
|
single nucleotide polymorphism adult acute lymphoblastic leukemia |
Additional relevant MeSH terms:
|
Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |