Clinical trial NCT00949052: Genetic Susceptibility and Risk of Second Cancers in Patients Who Have Undergone Stem Cell Transplant for Cancer
Official title: Radiation Sensitivity, DNA Repair, and Second Cancers.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Cancer
Keywords: cancer survivor
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
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous 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: 2009-07-30
Enrollment: 1000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who survived 100 days post-hematopoietic stem cell transplantation (HSCT)

Brief summary: RATIONALE: Identifying genes that increase a person's susceptibility to second cancers may help the study of cancer treatment.

PURPOSE: This study is looking at genetic susceptibility and risk of second cancers in patients who have undergone stem cell transplant for cancer.

Detailed description: OBJECTIVES:

Primary

* Determine whether genetic susceptibility (e.g., inherited differences in radiation sensitivity to normal tissue or genes of xenobiotic metabolism, nucleotide provision, or DNA repair) to the carcinogenic effects of radiotherapy, tobacco, and UV light modifies the risk of second malignant neoplasms (SMN) in patients with cancer treated with hematopoietic stem cell transplantation (HSCT).

Secondary

* Measure inherent sensitivity to radiotherapy via G_2 chromosome radiation sensitivity assay using B-cell lymphoblastoid cell lines derived from pre-HSCT cryopreserved peripheral blood mononuclear cells of patients with and without SMN.
* Measure the frequency of allelic variants of genes involved in xenobiotics metabolism, DNA repair, and provision of nucleotide pool and compare the frequencies among patients with and without SMN, determine the transmission of specific alleles of these genes from parents to patients, and correlate allelic variants of DNA repair and nucleotide provision in genes with in vitro radiation sensitivity.
* Evaluate the role of potentially carcinogenic environmental exposures (tobacco and sun light) pre- or post-HSCT in the risk of SMN and examine the association of these exposures with SMN and the interaction of these exposures with allelic variants of genes involved in xenobiotic metabolism, nucleotide provision, and DNA repair.

OUTLINE: Patients complete self-reported questionnaires and medical records are reviewed to collect information on UV light and tobacco exposure pre- and post-transplantation. Information is analyzed for association with second malignancy neoplasms.

Blood samples are collected from patients pre-hematopoietic stem cell transplantation and from their parents (when available) or other first-degree relatives for genetic biomarkers of susceptibility to second malignancies, DNA repair and provision nucleotide, genetic susceptibility to toxicity from combined cancer therapies, and environmental carcinogens.

PROJECTED ACCRUAL: A total of 1,000 patients (800 patients without second malignant neoplasms \[SMN\] and 200 patients with SMN) will be accrued for this study.

Eligibility criteria: Inclusion Criteria:

CASES are those who:

* Survived at least 100 days post-hematopoietic stem cell transplantation (HSCT).
* Developed an SMN after that time point.
* And received TBI as part of the preparative regimen.

CONTROLS are randomly selected:

* In a 4:1 ratio to cases from the same cohort of 100 day + survivors of HSCT who received TBI.
* Controls will be matched to the cases by race and primary diagnosis.
* In addition, they must have survived for at least the elapsed time between the case's HSCT and the secondary cancer, without development of an SMN.
* We are matching on primary diagnosis, as genotype or radiation sensitivity may predispose to specific primary cancers, as well as the SMNs.
* We are matching on race, as allele frequencies vary widely across ethnic groups.

Exclusion Criteria:

* Did not survive at least 100 days post-hematopoietic stem cell transplantation (HSCT).
* Did not develop an SMN after that time point.
* Did not receive TBI as part of the preparative regimen.

Primary outcomes:
measure: Genetic susceptibility to the carcinogenic effects of radiotherapy, tobacco, and UV light and risk of second malignant neoplasms (SMN)
timeFrame: At study entry
Secondary outcomes:
measure: Radiation sensitivity in B-cell lymphoblastoid cells
timeFrame: At study entry
measure: Allelic variants of genes involved in xenobiotics metabolism, DNA repair, and provision of nucleotide pool of patients with SMN compared to their first-degree relatives and patients without SMN
timeFrame: At study entry
measure: Role of potentially carcinogenic environmental exposures (tobacco and sun light) pre- and post-HSCT in the risk of SMN
timeFrame: At study entry
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Debra L. Friedman, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: