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

This study has been terminated.
(study closed prematurely upon PI's departure from VICC)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Madan Jagasia, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00957736
First received: August 11, 2009
Last updated: May 11, 2013
Last verified: May 2013
  Purpose

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 Intervention Phase
Cancer
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
Phase 1

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Targeted Single Nucleotide Polymorphisms (SNPs) to Classify Subtypes of Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Transplant.

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Ovarian Epithelial Cancer Acute Lymphoblastic Leukemia Lymphoma, Small Cleaved-cell, Diffuse Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Testicular Cancer Multiple Myeloma Chronic Myeloproliferative Disorders Hodgkin Lymphoma Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Homologous Wasting Disease Myelodysplastic/myeloproliferative Disease Neuroblastoma Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Juvenile Myelomonocytic Leukemia Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Kidney Cancer Renal Cancer Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Chronic Neutrophilic Leukemia Wilms' Tumor Hypereosinophilic Syndrome Acute Myeloid Leukemia, Childhood Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Gestational Trophoblastic Tumor Chronic Graft Versus Host Disease Ovarian Germ Cell Tumor Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome
U.S. FDA Resources

Further study details as provided by Vanderbilt-Ingram Cancer Center:

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. [ Time Frame: Upon data collection of final patient ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation of SNP profiles with predominant organ involvement and responsiveness of cGVHD to therapy [ Time Frame: Upon collection of data on final patient ] [ Designated as safety issue: No ]
  • Correlation of SNP profiles with survival endpoints [ Time Frame: Upon collection of data on final patient ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood


Enrollment: 252
Study Start Date: November 2008
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

allogeneic stem cell transplant patients

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00957736

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Madan Jagasia, MD Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Madan Jagasia, MD, Associate Professor of Medicine, Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00957736     History of Changes
Other Study ID Numbers: VICC BMT 0867, P30CA068485, VU-VICC-BMT-0867, IRB# 080995
Study First Received: August 11, 2009
Last Updated: May 11, 2013
Health Authority: United States: Federal Government

Keywords provided by Vanderbilt-Ingram Cancer Center:
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
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

Additional relevant MeSH terms:
Graft vs Host Disease
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Immune System Diseases
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on April 15, 2014