Myelodysplastic SyndromeNCT04515914
Clinical Relevance of DNMT and HDAC Gene SNP on the Response to Decitabine Therapy for Myelodysplastic Syndrome
An observational study of Myelodysplastic Syndrome, run by Samsung Medical Center at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- How many people
- 68 participants
- Where
- 1 siteSouth Korea
- Study dates
- Sep 2009to Nov 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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, plus additional MDS patients as a historical control.
- Inclusion Criteria:
- Decitabine treatment group
- Male and female aged 18 years or older.
- The patients diagnosed with (primary or secondary) MDS
- Patients with an IPSS score of ≥ Int-1
- Patients treated with Decitabine at least 1 cycles.
- Signed and dated informed consent before the start of genetic study using genomic DNA derived from blood sample.
- Historical control group
- Male and female aged 18 years or older.
- The patients diagnosed with (primary or secondary) MDS
- Exclusion Criteria:
- Patients diagnosed with acute myelogenous leukemia (AML, bone marrow stem cell counts exceeding 20%) or other progressive malignant diseases.
- Diagnosis of chronic myelomonocytic leukemia (CMML) or MDS/MPD excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Relevance of DNA Methyltransferase and Histone Deacetylase Gene Single Nucleotide Polymorphism in Myelodysplastic Syndrome
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.
Read the 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 manufacturer's instructions (www.sequenom.com; 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 2.5 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 primer(s), 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 0.05 unless otherwise stated. The statistical data will be obtained using an SAS version 9.1 (SAS Institute, Cary NC, USA). Followings are the endpoints for the study.
- 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.
- 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.
- Conditions
- Myelodysplastic Syndrome
- Keywords
- DNA methyltransferase gene, Histone deacetylase gene, Single nucleotide polymorphism, Decitabine, Myelodysplastic syndrome
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Decitabine therapy | The patients are treated with decitabine at least 1 cycles | |
| non-Decitabine therapy | The Patients are diagnosed as MDS and do not be treated with decitabine therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Measured: 18 months
Secondary outcomes (1)
Time to progression or hematologic improvement
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2020
- Study startSep 2009
- Primary completionOct 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Dong Hwan Kim, M.D.,Ph.D., Principal investigator, Division of Hematology and Oncology/Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04515914
- Sponsor's protocol ID
- 2009-04-012
- Status last verified
- Jan 2011
- First submitted
- 2 Jun 2010
- Last updated
- 17 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Relevance of DNA Methyltransferase and Histone Deacetylase Gene Single Nucleotide Polymorphism in Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT04515914
- Acronym / sponsor ID
- 2009-04-012
- Conditions
- Myelodysplastic Syndrome
- Keywords
- DNA methyltransferase gene, Histone deacetylase gene, Single nucleotide polymorphism, Decitabine, Myelodysplastic syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 17 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 manufacturer's instructions (www.sequenom.com; 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 2.5 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 primer(s), 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 0.05 unless otherwise stated. The statistical data will be obtained using an SAS version 9.1 (SAS Institute, Cary NC, USA). Followings are the endpoints for the study.
- 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.
- 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 design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Decitabine therapy | – | –The patients are treated with decitabine at least 1 cycles |
| non-Decitabine therapy | – | –The Patients are diagnosed as MDS and do not be treated with decitabine therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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, plus additional MDS patients as a historical control.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Overall response rate
Time frame: 18 months
1 secondary outcome
Time to progression or hematologic improvement
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dong Hwan Kim, M.D.,Ph.D. principal investigator
Division of Hematology and Oncology/Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myelodysplastic Syndrome, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2020.