Clinical trial NCT00957736: 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.
Study type: OBSERVATIONAL
Overall status: TERMINATED
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
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)
atypical chronic myeloid leukemia, BCR-ABL negative
blastic phase chronic myelogenous leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
juvenile myelomonocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
childhood myelodysplastic syndromes
chronic eosinophilic leukemia
primary myelofibrosis
chronic neutrophilic leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
myelodysplastic/myeloproliferative neoplasm, unclassifiable
poor prognosis metastatic gestational trophoblastic tumor
previously treated childhood rhabdomyosarcoma
previously treated myelodysplastic syndromes
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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-08-12
Enrollment: 252
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: allogeneic stem cell transplant patients

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.

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

Primary outcomes:
measure: 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.
timeFrame: Upon data collection of final patient
Secondary outcomes:
measure: Correlation of SNP profiles with predominant organ involvement and responsiveness of cGVHD to therapy
timeFrame: Upon collection of data on final patient
measure: Correlation of SNP profiles with survival endpoints
timeFrame: Upon collection of data on final patient
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Madan Jagasia, MD
role: PRINCIPAL_INVESTIGATOR
References: