Retroviral Vector Mediated Globin Gene Transfer to Correct Sickle Cell Anemia or Thalassemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborators:
Assisi Foundation
Doris Duke Charitable Foundation
University of Tennessee
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00669305
First received: April 28, 2008
Last updated: June 23, 2014
Last verified: June 2014

April 28, 2008
June 23, 2014
July 2007
July 2015   (final data collection date for primary outcome measure)
To develop retroviral vector mediated gene transfer as a potentially curative therapy for sickle cell anemia and β-thalassemia. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
The specific hypothesis to be tested is that a vector can be designed that achieves a therapeutic level of globin production in transduced cells.
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 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00669305 on ClinicalTrials.gov Archive Site
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Retroviral Vector Mediated Globin Gene Transfer to Correct Sickle Cell Anemia or Thalassemia
Experimental Evaluation of the Potential to Correct the Pathophysiology of Sickle Cell Anemia or Thalassemia by Retroviral Vector Mediated Globin Gene Transfer

Using sickle cell and thalassemia mouse models, researchers will evaluate the possibility of correcting these disorders by inserting healthy genetic material into the diseased blood cells. Human participants affected with sickle cell disease or thalassemia will donate bone marrow for use in the mouse models.

These studies are designed to evaluate the potential of retroviral vector mediated gene transfer 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 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. This study will evaluate whether a vector can be designed to achieve both a potentially therapeutic efficiency of gene transfer into repopulating cells and a potentially therapeutic level of globin gene expression in maturing erythroid cells.

Interventional
Not Provided
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Sickle Cell Anemia
  • Thalassemia
Genetic: Gene Therapy
Human participants affected with sickle cell disease or thalassemia will donate bone marrow for use in the mouse models
1
Intervention: Genetic: Gene Therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
28
July 2016
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with homozygous S/S disease or doubly heterozygous for S and β thalassemia who are 5 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 5 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
Both
Not Provided
No
Contact: Arthur W Nienhuis, MD 1-866-278-5833 info@stjude.org
United States
 
NCT00669305
EPSTRV, U54HL070590, P01HL053749, 201003
No
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Assisi Foundation
  • Doris Duke Charitable Foundation
  • University of Tennessee
Principal Investigator: Arthur W Nienhuis, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP