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 : April 7, 2023
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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.
- 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.
- 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.
- 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.
|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 Myelodysplastic Syndromes Myeloproliferative Diseases|
Participants will be individuals (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder. We propose to use genomics, transcriptomics, 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|
|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 :||July 2040|
|Estimated Study Completion Date :||July 2050|
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.
- 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.
- Number by type of inherited genetic aberrations associated with hematologic disorders [ Time Frame: 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 ]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, DNA sequencing, 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, yearly, and as needed until July 2050; and/or bone marrow aspirate at study entry, yearly and as needed until July 2050. ]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, yearly and as needed until July 2050; and/or bone marrow aspirate at study entry, yearly and as needed until July 2050. ]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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||Child, Adult, Older Adult|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Non-Probability Sample|
- 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.
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
|Contact: Marcin Wlodarski, MD, PhDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Marcin Wlodarski, MD, PhD 866-278-5833 email@example.com|
|Principal Investigator: Marcin Wlodarski, MD, PhD|
|Principal Investigator:||Marcin Wlodarski, MD, PhD||St. Jude Children's Research Hospital|
|Responsible Party:||St. Jude Children's Research Hospital|
|Other Study ID Numbers:||
|First Posted:||March 28, 2016 Key Record Dates|
|Last Update Posted:||April 7, 2023|
|Last Verified:||April 2023|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Whole genome sequencing
Pediatrics and hematology
DNA Repair-Deficiency Disorders
Anemia, Sickle Cell
Blood Coagulation Disorders
Bone Marrow Failure Disorders
Bone Marrow Diseases
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Blood Platelet Disorders