NCT00957736

Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant

Targeted Single Nucleotide Polymorphisms (SNPs) to Classify Subtypes of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Transplant.

• Status: Terminated
• Phase: —
• Study type: Observational
• Enrollment: 252 (actual)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2008-11-01
• Primary completion: 2008-12-01
• Completion: 2008-12-01
• First posted: 2009-08-12
• Last updated: 2013-05-14

Locations

3 sites across 1 country: United States