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
  Purpose

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.


Condition Intervention
Sickle Cell Anemia
Thalassemia
Genetic: Gene Therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Experimental Evaluation of the Potential to Correct the Pathophysiology of Sickle Cell Anemia or Thalassemia by Retroviral Vector Mediated Globin Gene Transfer

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 28
Study Start Date: July 2007
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Genetic: Gene Therapy
Human participants affected with sickle cell disease or thalassemia will donate bone marrow for use in the mouse models

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00669305

Contacts
Contact: Arthur W Nienhuis, MD 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Arthur W Nienhuis, MD    866-278-5833    info@stjude.org   
Principal Investigator: Arthur W Nienhuis, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Assisi Foundation
Doris Duke Charitable Foundation
University of Tennessee
Investigators
Principal Investigator: Arthur W Nienhuis, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00669305     History of Changes
Other Study ID Numbers: EPSTRV, U54HL070590, P01HL053749, 201003
Study First Received: April 28, 2008
Last Updated: June 23, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
Thalassemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 20, 2014