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Genetic Susceptibility and Risk of Second Cancers in Patients Who Have Undergone Stem Cell Transplant for Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00949052
First Posted: July 30, 2009
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Debra Friedman, Vanderbilt University Medical Center
  Purpose

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.


Condition Intervention
Cancer Genetic: DNA analysis Genetic: polymorphism analysis Other: laboratory biomarker analysis Other: medical chart review Other: questionnaire administration Procedure: assessment of therapy complications Procedure: evaluation of cancer risk factors

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Other
Time Perspective: Other
Target Follow-Up Duration: 1 Day
Official Title: Radiation Sensitivity, DNA Repair, and Second Cancers.

Resource links provided by NLM:


Further study details as provided by Debra Friedman, Vanderbilt University Medical Center:

Primary Outcome Measures:
  • Genetic susceptibility to the carcinogenic effects of radiotherapy, tobacco, and UV light and risk of second malignant neoplasms (SMN) [ Time Frame: At study entry ]

Secondary Outcome Measures:
  • Radiation sensitivity in B-cell lymphoblastoid cells [ Time Frame: At study entry ]
  • 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 [ Time Frame: At study entry ]
  • Role of potentially carcinogenic environmental exposures (tobacco and sun light) pre- and post-HSCT in the risk of SMN [ Time Frame: At study entry ]

Enrollment: 1000
Actual Study Start Date: January 2009
Estimated Study Completion Date: December 2020
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients who survived 100 days post-hematopoietic stem cell transplantation (HSCT)
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00949052


Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Debra L. Friedman, MD, MS Vanderbilt-Ingram Cancer Center
  More Information

Responsible Party: Debra Friedman, Associate Professor of Pediatrics, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT00949052     History of Changes
Other Study ID Numbers: VICC REACH 0901
P30CA068485 ( U.S. NIH Grant/Contract )
FHCRC-2023 ( Other Identifier: Fred Hutchinson Cancer Research Center )
IRB# 090032 ( Other Identifier: Vanderbilt University )
First Submitted: July 29, 2009
First Posted: July 30, 2009
Last Update Posted: May 30, 2017
Last Verified: May 2017

Keywords provided by Debra Friedman, Vanderbilt University Medical Center:
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

Additional relevant MeSH terms:
Neoplasms, Second Primary
Neoplasms