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Investigation of the Genetics of Hematologic Diseases

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ClinicalTrials.gov Identifier: NCT02720679
Recruitment Status : Recruiting
First Posted : March 28, 2016
Last Update Posted : October 23, 2018
Sponsor:
Collaborators:
Boston Children’s Hospital
Baylor College of Medicine
University of Memphis
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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 individuals with defined monogenic non-malignant blood diseases.
  • Identify genetic variants associated with treatment outcomes and toxicities for individuals with non-malignant blood disease.
  • Use transcriptomics, proteomics and metabolomics to investigate biomarkers for sickle cell disease (SCD) progression, paint events and the long-term cellular and molecular effects of hydroxyurea therapy.

Condition or disease
Bone Marrow Failure Syndromes Erythrocyte Disorder Leukocyte Disorder Hemostasis Blood Coagulation Disorder Sickle Cell Disease Dyskeratosis Congenita Diamond-Blackfan Anemia Congenital Thrombocytopenia Severe Congenital Neutropenia Fanconi Anemia

Detailed Description:

Participants will be individuals (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder. We propose to use genomics, trancriptomics, proteomics and metabolomic analysis coupled with family linkage studies to identify causal mutations in individuals with undefined hematologic disorders and to characterize genetic modifiers of defined monogenic blood diseases.

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.


Study Type : Observational [Patient Registry]
Estimated Enrollment : 1716 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: Investigation of the Genetics of Hematologic Diseases
Actual Study Start Date : June 17, 2016
Estimated Primary Completion Date : August 2026
Estimated Study Completion Date : August 2026


Group/Cohort
Study Participants
Participants will be (1) individuals with a non-malignant hematologic disorder confirmed or suspected to have a genetic basis, and (2) affected and unaffected family members of those individuals who are willing to provide clinical data and undergo genetic testing.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Biospecimen Retention:   Samples With DNA
Blood samples and bone marrow aspirate samples.


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants will be (1) individuals with a non-malignant hematologic disorder confirmed or suspected to have a genetic basis, and (2) affected and unaffected family members of those individuals who are willing to provide clinical data and undergo genetic testing.
Criteria

Inclusion Criteria:

  • An individual (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder.
  • A biologically-related individual to the identified proband to include: first, second or third degree relatives.

Exclusion Criteria:


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): NCT02720679


Contacts
Contact: Jeremie H. Estepp, MD 866-278-5833 referralinfo@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Jeremie Estepp, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Jeremie Estepp, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Boston Children’s Hospital
Baylor College of Medicine
University of Memphis
Investigators
Principal Investigator: Jeremie H. Estepp, MD St. Jude Children's Research Hospital

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT02720679     History of Changes
Other Study ID Numbers: INSIGHT-HD
First Posted: March 28, 2016    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:
Genetics
Whole genome sequencing
Pediatrics and hematology

Additional relevant MeSH terms:
Disease
Anemia
Anemia, Sickle Cell
Thrombocytopenia
Neutropenia
Hematologic Diseases
Fanconi Anemia
Fanconi Syndrome
Blood Coagulation Disorders
Hemostatic Disorders
Pancytopenia
Anemia, Diamond-Blackfan
Anemia, Aplastic
Hemoglobinuria, Paroxysmal
Dyskeratosis Congenita
Leukocyte Disorders
Pathologic Processes
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Blood Platelet Disorders
Agranulocytosis
Leukopenia
Anemia, Hypoplastic, Congenital
Bone Marrow Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Renal Tubular Transport, Inborn Errors
Kidney Diseases