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Bone Marrow for Hemoglobinopathy Research

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ClinicalTrials.gov Identifier: NCT00669305
Recruitment Status : Recruiting
First Posted : April 30, 2008
Last Update Posted : February 15, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Assisi Foundation
University of Tennessee
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Tracking Information
First Submitted Date April 28, 2008
First Posted Date April 30, 2008
Last Update Posted Date February 15, 2019
Actual Study Start Date May 15, 2008
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 3, 2015)
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 ]
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.
Original Primary Outcome Measures
 (submitted: April 28, 2008)
To develop retroviral vector mediated gene transfer as a potentially curative therapy for sickle cell anemia and β-thalassemia. The specific hypothesis to be tested is that a vector can be designed that achieves a therapeutic level of globin transgene [ Time Frame: 4 years ]
Change History Complete list of historical versions of study NCT00669305 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Bone Marrow for Hemoglobinopathy Research
Official Title Bone Marrow for Hemoglobinopathy Research
Brief Summary 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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Stem Cells through Bone Marrow Aspiration
Sampling Method Probability Sample
Study Population Patients with Sickle Cell Anemia or Thalassemia
Condition
  • Sickle Cell Anemia
  • Thalassemia
Intervention Not Provided
Study Groups/Cohorts Cohort 1
Human participants affected with sickle cell disease or thalassemia will donate bone marrow for use in experimental models
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 28, 2008)
28
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2024
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

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.

    1. 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.
    2. 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
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts
Contact: Mitchell J. Weiss, MD, PhD 866-278-5833 referralinfo@stjude.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00669305
Other Study ID Numbers BMR
U54HL070590 ( U.S. NIH Grant/Contract )
P01HL053749 ( U.S. NIH Grant/Contract )
201003 ( Other Identifier: Doris Duke Foundation )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party St. Jude Children's Research Hospital
Study Sponsor St. Jude Children's Research Hospital
Collaborators
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Assisi Foundation
  • University of Tennessee
Investigators
Principal Investigator: Mitchell J. Weiss, MD, PhD St. Jude Children's Research Hospital
PRS Account St. Jude Children's Research Hospital
Verification Date February 2019