Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant
Study Details
Study Description
Brief Summary
RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to chronic graft-versus-host disease in patients who have undergone donor stem cell transplant.
PURPOSE: This phase I trial is studying chronic graft-versus-host disease in patients who have undergone donor stem cell transplant.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
OBJECTIVES:
- To determine and define the biological basis of different subtypes of chronic graft-vs-host disease using a targeted single nucleotide polymorphisms approach in patients who have undergone allogeneic stem cell transplantation.
OUTLINE: Two important aspects of the methodologies that will be employed for the analysis of SNPs associated with GVHD are throughput efficiency to be able to perform the assays on a reasonable number of samples as well as having the ability to add or remove SNPs to the assay panel. While a genome-wide association study to identify variants associated with GVHD would offer an unbiased approach, our patient cohort size would not allow significant statistical power in the study. Therefore, a more targeted approach using two established technologies is proposed.
The Sequenome assay uses the unique combination of a single-base primer extension assay incorporating one of four modified nucleotides. The four modified nucleotides each have a unique mass that allows them to be distinguished from one another using mass spectrometry. Each SNP is determined analyzing the primer extension product from a PCR amplicon that surrounds the SNP of interest. The development of each assay involves designing flanking PCR primers and an internal extension assay using web-based software provided by Sequenome. The assays can be designed to analyze up to 30 SNPs in a single reaction, providing a customizable, efficient and high-throughput assay for SNPs of interest.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Allogeneic stem cell transplant Stem cells from a genetically non-identical donor transplanted into a patient. |
Genetic: polymorphism analysis
Will assess the SNPs present in both the donor and to host and correlate the SNPs with outcome based in the NIH consensus criteria for cGVHD. Candidate SNPs will include but are not limited to TGF-β18, mannose binding lectin19, myeloperoxidase, HSP 70, minor histocompatability antigens, KIR, CCL513, NOD2/CARD1512, TNFα11, TNF R II, IL-1010, 11, IL-1317, IL-620, IFN-γ20, IL-1 RA21, IL-2315, and IL-1516. Other candidate genes will be assessed on current review of the literature and candidate SNPs will be added based on their relationship to aGVHD, cGVHD, autoimmune disease, pharmacogenetics, and other immunologic processes. The genes will be assessed for gene frequency using the HapMap and SNP databases prior to statistical analysis.
Other: laboratory biomarker analysis
Will assess the SNPs present in both the donor and to host and correlate the SNPs with outcome based in the NIH consensus criteria for cGVHD. Candidate SNPs will include but are not limited to TGF-β18, mannose binding lectin19, myeloperoxidase, HSP 70, minor histocompatability antigens, KIR, CCL513, NOD2/CARD1512, TNFα11, TNF R II, IL-1010, 11, IL-1317, IL-620, IFN-γ20, IL-1 RA21, IL-2315, and IL-1516. Other candidate genes will be assessed on current review of the literature and candidate SNPs will be added based on their relationship to aGVHD, cGVHD, autoimmune disease, pharmacogenetics, and other immunologic processes. The genes will be assessed for gene frequency using the HapMap and SNP databases prior to statistical analysis.
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Outcome Measures
Primary Outcome Measures
- To study the SNP profiles of a select group of candidate non-HLA genes among various cGVHD subtypes. Patients will be stratified as having classic cGVHD vs. non-classic GVHD for initial analyses. [Upon data collection of final patient]
Secondary Outcome Measures
- Correlation of SNP profiles with predominant organ involvement and responsiveness of cGVHD to therapy [Upon collection of data on final patient]
- Correlation of SNP profiles with survival endpoints [Upon collection of data on final patient]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Underwent prior matched related or unrelated allogeneic stem cell transplantation (SCT)
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Presence OR absence of chronic graft-vs-host disease after day 100 and alive after day 180 post-transplantation
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No T-cell depleted SCT, cord blood transplantation, mismatched allogeneic transplantation, or autologous transplantation
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Available recipient and donor DNA (samples collected from the Vanderbilt University or the Fred Hutchinson Cancer Center tissue bank)
PATIENT CHARACTERISTICS:
- Not specified
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vanderbilt-Ingram Cancer Center - Cool Springs | Nashville | Tennessee | United States | 37064 |
| 2 | Vanderbilt-Ingram Cancer Center at Franklin | Nashville | Tennessee | United States | 37064 |
| 3 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232-6838 |
Sponsors and Collaborators
- Vanderbilt-Ingram Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Madan Jagasia, MD, Vanderbilt-Ingram Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VICC BMT 0867
- P30CA068485
- VU-VICC-BMT-0867
- IRB# 080995