Ignite Creation Date:
2024-05-06 @ 3:05 PM
Last Modification Date:
2024-10-26 @ 1:42 PM
Study NCT ID:
NCT04515914
Status:
COMPLETED
Last Update Posted:
2020-08-17
First Post:
2010-06-02
Brief Title:
Clinical Relevance of DNMT and HDAC Gene SNP on the Response to Decitabine Therapy for Myelodysplastic Syndrome
Sponsor:
Samsung Medical Center
Organization:
Samsung Medical Center
Study Overview
Official Title:
Clinical Relevance of DNA Methyltransferase and Histone Deacetylase Gene Single Nucleotide Polymorphism in Myelodysplastic Syndrome
Status:
COMPLETED
Status Verified Date:
2011-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Recent investigations have demonstrated that DNMT gene polymorphisms can contribute to the inter-individual variants in DNMT expression Accordingly we hypothesized that the DNMT and HDAC genes SNPs could predict the outcomes of decitabine therapy for myelodysplastic syndrome Prospective collection of DNA from peripheral blood will be performed in the patients with MDS before commencement of decitabine therapy We will evaluate the efficacy decitabine therapy according to the DNMT or HDAC gene SNPs in terms of following parameters 1 hematolotic response HR or improvement HI or requirement of decitabine dose to achieve HR or HI 2 complete CR or partial response PR or requirement of decitabine dose to achieve CR or PR and 3 time to relapse or progression of MDS
The objective of this study is 1 to determine genotypes from DNA samples from MDS patients receiving Decitabine therapy 2 to determine the association of clinical outcomes HR HI CR PR or time to progression to leukemia following decitabine therapy with DNMT or HDAC genotypes and 3 to analyze the impact of cytogenetic risk on the response or leukemic evolution following decitabine therapy for MDS
The objective of this study is 1 to determine genotypes from DNA samples from MDS patients receiving Decitabine therapy 2 to determine the association of clinical outcomes HR HI CR PR or time to progression to leukemia following decitabine therapy with DNMT or HDAC genotypes and 3 to analyze the impact of cytogenetic risk on the response or leukemic evolution following decitabine therapy for MDS
Detailed Description:
This study will include the patients who signed the subject informed consent form among the patients with MDS who were chosen to be treated with Decitabine Part I plus additional 140 MDS patients as a historical control Part II Approximately 68 patients will be included who satisfy the following inclusion and exclusion criteria in the Part I study
Prospective collection of DNA from peripheral blood will be performed in the patients with MDS before commencement of decitabine therapy We will evaluate the efficacy decitabine therapy according to the DNMT or HDAC gene SNPs in terms of following parameters 1 hematolotic response HR or improvement HI or requirement of decitabine dose to achieve HR or HI 2 complete CR or partial response PR or requirement of decitabine dose to achieve CR or PR and 3 time to relapse or progression of MDS
Genotyping will be undertaken using the Sequenom iPLEX platform according to the manufacturers instructions wwwsequenomcom Sequenom Inc San Diego CA USA Whole blood samples will be obtained according to the declaration of Helsinki DNA will be extracted using the Puregene DNA purification Kit Gentra Systems Inc Minneapolis MN USA The detection of SNPs will be performed by the analysis of primer extension products generated from previously amplified genomic DNA using a Sequenom chip-based matrix-assisted laser desorption ionization time-of-flight MALDI-TOF mass spectrometry platform Multiplex SNP assays will be designed using SpectroDesigner software Sequenom Ninety-six well plates containing 25 ng DNA in each well will be amplified by PCR following the specifications of Sequenom Unincorporated nucleotides in the PCR product will be deactivated using shrimp alkaline phosphatase Allele discrimination reactions will be conducted by adding the extension primers DNA polymerase and a cocktail mixture of deoxynucleotide triphosphates and di-deoxynucleotide triphosphates to each well MassExtend clean resin Sequenom will be added to the mixture to remove extraneous salts that could interfere with MALDI-TOF analysis The primer extension products will be then cleaned and spotted onto a SpectroChip Genotypes will be determined by spotting an aliquot of each sample onto a 384 SpectroChip Sequenom which is subsequently read by the MALDI-TOF mass spectrometer
All statistical tests will be two-sided with the significance level set as 005 unless otherwise stated The statistical data will be obtained using an SAS version 91 SAS Institute Cary NC USA Followings are the endpoints for the study
1 Primary endpoint evaluation data
Response rate A response rate will be obtained and its confidence interval estimated to be evaluated through chi-square test If the main endpoints which may influence the final evaluation must be controlled stratified analysis Cochran-Mantel-Haenzel etc will be conducted If all the subjects characteristic endpoints must be controlled the logistic regression model will be used for analysis
2 Secondary endpoint evaluation data
Overall survival survival will be evaluated from the registration day to death through Kaplan-Meier method
Progression free survival The time of progression from MDS to AML and death from any cause Progression free survival will be analyzed through Kaplan-Meier method
Prospective collection of DNA from peripheral blood will be performed in the patients with MDS before commencement of decitabine therapy We will evaluate the efficacy decitabine therapy according to the DNMT or HDAC gene SNPs in terms of following parameters 1 hematolotic response HR or improvement HI or requirement of decitabine dose to achieve HR or HI 2 complete CR or partial response PR or requirement of decitabine dose to achieve CR or PR and 3 time to relapse or progression of MDS
Genotyping will be undertaken using the Sequenom iPLEX platform according to the manufacturers instructions wwwsequenomcom Sequenom Inc San Diego CA USA Whole blood samples will be obtained according to the declaration of Helsinki DNA will be extracted using the Puregene DNA purification Kit Gentra Systems Inc Minneapolis MN USA The detection of SNPs will be performed by the analysis of primer extension products generated from previously amplified genomic DNA using a Sequenom chip-based matrix-assisted laser desorption ionization time-of-flight MALDI-TOF mass spectrometry platform Multiplex SNP assays will be designed using SpectroDesigner software Sequenom Ninety-six well plates containing 25 ng DNA in each well will be amplified by PCR following the specifications of Sequenom Unincorporated nucleotides in the PCR product will be deactivated using shrimp alkaline phosphatase Allele discrimination reactions will be conducted by adding the extension primers DNA polymerase and a cocktail mixture of deoxynucleotide triphosphates and di-deoxynucleotide triphosphates to each well MassExtend clean resin Sequenom will be added to the mixture to remove extraneous salts that could interfere with MALDI-TOF analysis The primer extension products will be then cleaned and spotted onto a SpectroChip Genotypes will be determined by spotting an aliquot of each sample onto a 384 SpectroChip Sequenom which is subsequently read by the MALDI-TOF mass spectrometer
All statistical tests will be two-sided with the significance level set as 005 unless otherwise stated The statistical data will be obtained using an SAS version 91 SAS Institute Cary NC USA Followings are the endpoints for the study
1 Primary endpoint evaluation data
Response rate A response rate will be obtained and its confidence interval estimated to be evaluated through chi-square test If the main endpoints which may influence the final evaluation must be controlled stratified analysis Cochran-Mantel-Haenzel etc will be conducted If all the subjects characteristic endpoints must be controlled the logistic regression model will be used for analysis
2 Secondary endpoint evaluation data
Overall survival survival will be evaluated from the registration day to death through Kaplan-Meier method
Progression free survival The time of progression from MDS to AML and death from any cause Progression free survival will be analyzed through Kaplan-Meier method
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None