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

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00957736
• Other study ID #: VICC BMT 0867
• Secondary ID: P30CA068485VU-VI
• Status: Terminated
• Phase: Phase 1
• First received: August 11, 2009
• Last updated: May 11, 2013
• Start date: November 2008
• Est. completion date: December 2008

Study information

• Verified date: May 2013
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 252
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

DISEASE CHARACTERISTICS:

• Underwent prior matched related or unrelated allogeneic stem cell transplantation (SCT)

• Presence OR absence of chronic graft-vs-host disease after day 100 and alive after day 180 post-transplantation

• No T-cell depleted SCT, cord blood transplantation, mismatched allogeneic transplantation, or autologous transplantation

• 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

Study Design

Observational Model: Case-Only, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Cancer
• Graft vs Host Disease

Intervention

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-ß18, mannose binding lectin19, myeloperoxidase, HSP 70, minor histocompatability antigens, KIR, CCL513, NOD2/CARD1512, TNFa11, TNF R II, IL-1010, 11, IL-1317, IL-620, IFN-?20, 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-ß18, mannose binding lectin19, myeloperoxidase, HSP 70, minor histocompatability antigens, KIR, CCL513, NOD2/CARD1512, TNFa11, TNF R II, IL-1010, 11, IL-1317, IL-620, IFN-?20, 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.

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Correlation of SNP profiles with predominant organ involvement and responsiveness of cGVHD to therapy		Upon collection of data on final patient	No
Secondary	Correlation of SNP profiles with survival endpoints		Upon collection of data on final patient	No