Clinical Trial: Investigation of the Genetics of Hematologic Diseases

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Investigation of the Genetics of Hematologic Diseases

Brief Summary:

The purpose of this study is to collect and store samples and health information for current and future research to learn more about the causes and treatment of blood diseases. This is not a therapeutic or diagnostic protocol for clinical purposes. Blood and bone marrow as well as health information will be used to study and learn about blood diseases by using genetic and/or genomic research. In general, genetic research studies specific genes of an individual; genomic research studies the complete genetic makeup of an individual.

It is not known why many people have blood diseases, because not all genes causing these diseases have been found. It is also not known why some people with the same disease are sicker than others, but this may be related to their genes. By studying the genomes in individuals with blood diseases and their family members, the investigators hope to learn more about how diseases develop and respond to treatment which may provide new and better ways to diagnose and treat blood diseases.

Primary Objective:

  • Establish a repository of DNA and cryopreserved blood cells with linked clinical information from individuals with non-malignant blood diseases and biologically-related family members in order to conduct genomic and functional studies as outlined in the secondary objectives.

Secondary Objectives:

Utilizing the biorepository, investigators aim to:

  • Identify novel mutations that associate with disease status in individuals with unexplained non-malignant blood diseases.
  • Identify modifier genes in indivi

    Detailed Summary:

    Participants will be individuals (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder.

    A detailed medical history will be obtained, including demographic information for each proband. For each identified biologically-related family member, a medical history questionnaire will be obtained. The family history and pedigree will be reviewed in conjunction with a geneticist/genetic counselor. The implications of genetic testing will be explained. If participants consent for future contact, this will take place annually for updates on medical and family history.

    All probands will provide peripheral blood samples, and probands who are undergoing a bone marrow aspirate/biopsy for clinical purposes will provide additional aspirates. Biological family members will provide peripheral blood samples as a source for DNA.


    Sponsor: St. Jude Children's Research Hospital

    Current Primary Outcome: Percent of participants who agree to participate [ Time Frame: Day 1, at enrollment ]

    It is estimated that approximately 30% of participants (proband) approached for this study will agree to participate and that each proband will have approximately five biologically-related family members who agree to participate.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Number by type of inherited genetic aberrations associated with hematologic disorders [ Time Frame: Blood drawn at study entry and up to 5 occasions (up to 5 years after enrollment); and/or bone marrow aspirate at study entry and yearly up to 3 occasions (up to 5 years after enrollment) ]
      Germ-line DNA samples from study participants will be extracted and analyzed in order to identify inherited genetic aberrations associated with hematologic disorders. Specific modalities of genomic testing will be case specific. Relevant tests may involve SNP arrays to assess copy number variation, WGS, WES, targeted sequencing of specific candidate genes, RNA-sequencing, X-chromosome inactivation studies, ChIP sequencing and/or other tests. Genetic linkage analyses may be performed using a variety of technologies including high-density SNP arrays, WGS and specific analysis of selected target genes in validation studies.
    • Number by type of modifier genes [ Time Frame: Blood drawn at study entry and up to 5 occasions (up to 5 years after enrollment); and/or bone marrow aspirate at study entry and yearly up to 3 occasions (up to 5 years after enrollment) ]
      Investigators seek to identify modifier genes in individuals in the study population. Methods of analysis will be similar to those for Outcome Measure #2.
    • Number by type of genetic variants [ Time Frame: Blood drawn at study entry and up to 5 occasions (up to 5 years after enrollment); and/or bone marrow aspirate at study entry and yearly up to 3 occasions (up to 5 years after enrollment) ]
      Investigators seek to identify genetic variants associated with treatment outcomes and toxicities in the study population. Methods of analysis will be similar to those for Outcome Measure #2.


    Original Secondary Outcome: Same as current

    Information By: St. Jude Children's Research Hospital

    Dates:
    Date Received: March 16, 2016
    Date Started: June 17, 2016
    Date Completion: August 31, 2026
    Last Updated: March 1, 2017
    Last Verified: September 2016