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

August 14, 2018 updated by: Debra Friedman, Vanderbilt-Ingram Cancer Center

Radiation Sensitivity, DNA Repair, and Second Cancers.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients who survived 100 days post-hematopoietic stem cell transplantation (HSCT)

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
Radiation sensitivity in B-cell lymphoblastoid cells
Time Frame: At study entry
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
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
At study entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Debra L. Friedman, MD, MS, Vanderbilt-Ingram Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2009

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

February 1, 2018

Study Registration Dates

First Submitted

July 29, 2009

First Submitted That Met QC Criteria

July 29, 2009

First Posted (Estimate)

July 30, 2009

Study Record Updates

Last Update Posted (Actual)

August 16, 2018

Last Update Submitted That Met QC Criteria

August 14, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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