- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00669305
Bone Marrow for Hemoglobinopathy Research
February 21, 2020 updated by: St. Jude Children's Research Hospital
Human participants affected with sickle cell disease or thalassemia will donate bone marrow for use in experimental laboratory models to study potential new treatments.
This is an observational study using bone marrow from human participants.
The investigators will use sickle cell and thalassemia mouse models to observe and evaluate the possibility of correcting these disorders through genetic alterations or drug treatment.
Study Overview
Status
Completed
Conditions
Detailed Description
These studies are designed to evaluate the potential of retroviral vector mediated gene transfer, gene editing, or drug treatment to correct the pathophysiology of sickle cell anemia and β-thalassemia.
CD34+ cells purified from bone marrow of research participants with a sickle cell syndrome or a thalassemia syndrome will be subjected to genetic editing, drug treatment, or transduced with retroviral vectors containing γ-globin coding sequences under the control of the β-globin gene promoter and including various regulatory elements chosen to enhance gene expression and to insulate regulatory elements from cellular genes at or near the integration sites.
The efficiency of gene transfer and the function of the globin transgene will be evaluated in erythroid cells derived from transduced progenitors and from the progenitors in the bone marrow of immunodeficient mice engrafted with transduced, primitive hematopoietic cells.
The hypothesis to be tested in this research is that a gene therapy vector, gene editing strategy, or drug modality can be designed to achieve a potentially therapeutic level of globin gene expression in maturing erythroid cells.
Study Type
Observational
Enrollment (Actual)
26
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
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
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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
Probability Sample
Study Population
Patients with Sickle Cell Anemia or Thalassemia
Description
Inclusion Criteria:
- Patients with homozygous S/S disease or doubly heterozygous for S and β thalassemia who are 2 years or older are eligible. Patients with HbE- β- thalassemia or homozygous (severe) β-thalassemia are also eligible. Patients with thalassemia include those who are transfusion dependent (major) or severely anemic but relatively transfusion independent (intermedia). Diagnostic criteria include standard hematological parameters, red cell indices, hemoglobin electrophoresis and quantitative determination of HbF and HbA2.
- Patients are eligible for participation in the protocol only if they are currently clinically stable and have been free of all acute disease manifestations for a minimum of 14 days.
- Patients may participate while continuing their current therapeutic regimen including regular transfusion therapy or hydroxyurea administration.
In general, two categories of patients will be considered as research participants in this protocol.
- Patients who are 18 years or older and therefore able to provide informed consent will be eligible. Such individuals will be recruited from among patients followed at SJCRH. In addition, individuals followed in an outside clinic who are recruited will be asked to come to the Hematology Clinic at SJCRH to enroll and have the procedure performed. Alternatively, if a patient who is 18 or older is to undergo a diagnostic or surgical procedure under general anesthesia, and they agree to participate in the study, the bone marrow aspirate will be obtained at that time.
- Patients between the ages of 2 and 17 years who are scheduled for a diagnostic or surgical procedure at SJCRH or LeBonheur Children's Medical Center for which sedation or general anesthesia is indicated will be eligible for protocol enrollment. A bone marrow aspiration will be performed during the sedation or general anesthesia for the diagnostic or surgical procedure.
Exclusion Criteria:
- Active, acute manifestations of sickle cell disease including painful crisis, acute chest syndrome, cerebrovascular events or active infection.
- Pregnant women will not be eligible for study enrollment.
- Inability or unwillingness of the research participant or legal guardian/representative to give written informed consent will preclude enrollment on this research protocol.
- Platelet count < 150,000/mm^3
- Neutrophil count < 2000/mm^3 (unless on hydroxyurea therapy)
- Neutrophil count < 1000/mm^3 for patients on hydroxyurea therapy
- Prothrombin Time > 17 seconds
- Partial thromboplastin Time > 43 seconds
- History of excessive bleeding in the context of previous procedures including surgery and dental extractions
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: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Cohort 1
Human participants affected with sickle cell disease or thalassemia will donate bone marrow for use in experimental models
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of successful achievement of therapeutic level in mouse models resulting from retroviral vector mediated gene transfer, gene editing or drug treatment.
Time Frame: 4 years
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The specific hypothesis to be tested is that a gene therapy vector, gene editing strategy, or drug modality can be designed that achieves a therapeutic level of globin production in transduced cells in mouse models.
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4 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Mitchell J. Weiss, MD, PhD, St. Jude Children's Research Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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)
May 15, 2008
Primary Completion (Actual)
August 29, 2019
Study Completion (Actual)
August 29, 2019
Study Registration Dates
First Submitted
April 28, 2008
First Submitted That Met QC Criteria
April 28, 2008
First Posted (Estimate)
April 30, 2008
Study Record Updates
Last Update Posted (Actual)
February 25, 2020
Last Update Submitted That Met QC Criteria
February 21, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BMR
- U54HL070590 (U.S. NIH Grant/Contract)
- P01HL053749 (U.S. NIH Grant/Contract)
- 201003 (Doris Duke Foundation)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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