Investigation of the Genetics of Hematologic Diseases

NCT02720679 | Recruiting

• 1 other identifier: INSIGHT-HD
• Study Type: observational
• Target: 1,716
• Locations: 1 country
• Sites: 1

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, bone marrow, hair follicles, nail clippings, urine, saliva and buccal swabs, left over tissue, 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 conjunction with the existing St. Jude biorepository, to conduct genomic and functional studies to facilitate secondary objectives. Secondary Objectives:
• Utilize next generation genomic sequencing technologies to Identify novel genetic alternations that associate with disease status in individuals with unexplained non-malignant blood diseases.
• Use genomic approaches to identify modifier genes in individuals with defined monogenic non-malignant blood diseases.
• Use genomic approaches to identify genetic variants associated with treatment outcomes and toxicities for individuals with non-malignant blood disease.
• Use single cell genomics, transcriptomics, proteomics and metabolomics to investigate biomarkers for disease progression, sickle cell disease (SCD) pain events and the long-term cellular and molecular effects of hydroxyurea therapy.
• Using longitudinal assessment of clinical and genetic, study the long-term outcomes and evolving genetic changes in non-malignant blood diseases. Exploratory Objectives
• Determine whether analysis of select patient-derived bone marrow hematopoietic progenitor/stem (HSPC) cells or induced pluripotent stem (iPS) cells can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.
• Determine whether analysis of circulating mature blood cells and their progenitors from selected patients with suspected or proven genetic hematological disorders can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.

Conditions

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; Myelodysplastic Syndromes; Myeloproliferative Diseases

Keywords

Genetics; Whole genome sequencing; Pediatrics and hematology

Outcome Measures

Primary Outcomes (1)

• Percent of participants who agree to participate

  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.

  Day 1, at enrollment

Secondary Outcomes (3)

• Number by type of inherited genetic aberrations associated with hematologic disorders

  Blood drawn at study entry, yearly and as needed until July 2050; and/or bone marrow aspirate at study entry, yearly and as needed until July 2050

• Number by type of modifier genes

  Blood drawn at study entry, yearly, and as needed until July 2050; and/or bone marrow aspirate at study entry, yearly and as needed until July 2050.

• Number by type of genetic variants

  Blood drawn at study entry, yearly and as needed until July 2050; and/or bone marrow aspirate at study entry, yearly and as needed until July 2050.

Study Arms (1)

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.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• None

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Boston Children's Hospital: collaborator
• University of Memphis: collaborator
• Monroe Carell Jr. Children's Hospital at Vanderbilt: collaborator
• Baylor College of Medicine: collaborator
• Children's Hospital of Philadelphia: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• INSIGHT-HD Study Summary
• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, bone marrow aspirate samples, nail clippings, urine, saliva, buccal smears and hair follicles, left over tissue.

MeSH Terms

Conditions

Bone Marrow Failure Disorders; Leukocyte Disorders; Blood Coagulation Disorders; Anemia, Sickle Cell; Dyskeratosis Congenita; Anemia, Diamond-Blackfan; Neutropenia, Severe Congenital, Autosomal Recessive 3; Fanconi Anemia; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Congenital Bone Marrow Failure Syndromes; Skin Abnormalities; Congenital Abnormalities; Genetic Diseases, X-Linked; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Marcin Wlodarski, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcin Wlodarski, MD, PhD

CONTACT

866-278-5833; referralinfo@stjude.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 28, 2016
• Study Start: June 17, 2016
• Primary Completion (Estimated): July 1, 2040
• Study Completion (Estimated): July 1, 2050
• Last Updated: November 4, 2025

Record last verified: 2025-11

Locations

US (1)