Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant
Official Title
Targeted Single Nucleotide Polymorphisms (SNPs) to Classify Subtypes of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Transplant.
Acronym
Not provided
Organization
Vanderbilt-Ingram Cancer CenterOTHER
Status Module
Record Verification Date
May 2013
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
study closed prematurely upon PI's departure from VICC
Expanded Access Info
No
Start Date
Nov 2008
Primary Completion Date
Dec 2008Actual
Completion Date
Dec 2008Actual
First Submitted Date
Aug 11, 2009
First Submission Date that Met QC Criteria
Aug 11, 2009
First Posted Date
Aug 12, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Not provided
Results First Submitted that Met QC Criteria
Not provided
Results First Posted Date
Not provided
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 11, 2013
Last Update Posted Date
May 14, 2013Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Madan Jagasia, MD, Associate Professor of Medicine, Medical Oncologist, Vanderbilt-Ingram Cancer CenterPrincipal Investigator
Lead Sponsor
Vanderbilt-Ingram Cancer CenterOTHER
Collaborators
Name
Class
National Cancer Institute (NCI)
NIH
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
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 Module
Conditions
Cancer
Keywords
graft versus host disease
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult Hodgkin lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage III small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
Design Module
Study Type
Observational
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
No
Target Follow-Up Duration
Not provided
Phases
Not provided
Interventional Study Design
Allocation
Not provided
Intervention Model
Biospecimen
Retention
Enrollment
252Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Allogeneic stem cell transplant
Stem cells from a genetically non-identical donor transplanted into a patient.
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
Interventions
Name
Type
Description
Arm Group Labels
Other Names
polymorphism analysis
Genetic
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.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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 Outcomes
Measure
Description
Time Frame
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
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
Not provided
Maximum Age
Not provided
Standard Ages
ChildAdultOlder Adult
Study Population
allogeneic stem cell transplant patients
Sampling Method
Non-Probability Sample
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Madan Jagasia, MD
Vanderbilt-Ingram Cancer Center
Principal Investigator
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville
Tennessee
37064
United States
Vanderbilt-Ingram Cancer Center at Franklin
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
ID
Term
D009369
Neoplasms
D006086
Graft vs Host Disease
D002051
Burkitt Lymphoma
D016403
Lymphoma, Large B-Cell, Diffuse
D008228
Lymphoma, Non-Hodgkin
D006689
Hodgkin Disease
D016400
Lymphoma, Large-Cell, Immunoblastic
D054198
Precursor Cell Lymphoblastic Leukemia-Lymphoma
D008224
Lymphoma, Follicular
D020522
Lymphoma, Mantle-Cell
D018442
Lymphoma, B-Cell, Marginal Zone
D015451
Leukemia, Lymphocytic, Chronic, B-Cell
D054739
Dendritic Cell Sarcoma, Interdigitating
D016410
Lymphoma, T-Cell, Cutaneous
D012008
Recurrence
D009182
Mycosis Fungoides
D012751
Sezary Syndrome
D015465
Ancestor Terms
ID
Term
D007154
Immune System Diseases
D020031
Epstein-Barr Virus Infections
D006566
Herpesviridae Infections
D004266
DNA Virus Infections
Browse Leaves
Not provided
Browse Branches
Not provided
Intervention Browse Module
MeSH Terms
ID
Term
D054458
Amplified Fragment Length Polymorphism Analysis
Ancestor Terms
ID
Term
D016172
DNA Fingerprinting
D005821
Genetic Techniques
D008919
Investigative Techniques
D016133
Polymerase Chain Reaction
Browse Leaves
Not provided
Browse Branches
Not provided
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
noncontiguous (NC) stage II adult Burkitt lymphoma
NC stage II adult diffuse large cell lymphoma
NC stage II adult diffuse mixed cell lymphoma
NC stage II adult diffuse small cleaved cell lymphoma
NC stage II adult immunoblastic large cell lymphoma
NC stage II adult lymphoblastic lymphoma
NC stage II grade 1 follicular lymphoma
NC stage II grade 2 follicular lymphoma
NC stage II grade 3 follicular lymphoma
NC stage II mantle cell lymphoma
NC stage II marginal zone lymphoma
NC stage II small lymphocytic lymphoma
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent Wilms tumor and other childhood kidney tumors
recurrent childhood rhabdomyosarcoma
recurrent neuroblastoma
recurrent ovarian epithelial cancer
recurrent ovarian germ cell tumor
recurrent malignant testicular germ cell tumor
secondary myelodysplastic syndromes
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
stage III malignant testicular germ cell tumor
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
refractory multiple myeloma
Not provided
Intervention Model Description
Not provided
Primary Purpose
Not provided
Observational Model
Case-Only
Time Perspective
Retrospective
Masking Info
No data available
No data is available for this block.
Samples With DNA
Description
blood
Allogeneic stem cell transplant
laboratory biomarker analysis
Other
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.