Retroviral Vector Mediated Globin Gene Transfer to Correct Sickle Cell Anemia or Thalaassemia - Full Text View

Sponsored by:	St. Jude Children's Research Hospital
Information provided by:	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:	NCT00669305

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

Genetics Home Reference related topics: beta thalassemia sickle cell disease

MedlinePlus related topics: Anemia Sickle Cell Anemia Thalassemia

U.S. FDA Resources

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

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. 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 ]

Estimated Enrollment:	28
Study Start Date:	July 2007
Estimated Primary Completion Date:	July 2011 (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

Ages Eligible for Study:	5 Years to 17 Years
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, the protocol will be opened in the clinic of the University of Tennessee Cancer Center where adult patients with sickle cell disease are followed and at the Diggs-Kraus Sickle Cell Clinic in the Regional Medical Center. Individuals followed in an outside clinic who are recruited may be enrolled on the protocol and have the procedure in the clinic office or may be asked to come to the Translational Trials Unit 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, 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/mm3
Neutrophil count < 2000/mm3
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

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

Investigators

Principal Investigator:

Arthur W Nienhuis, MD

St. Jude Children's Research Hospital

More Information

Related Info This link exits the ClinicalTrials.gov site

Responsible Party:	United States: Food and Drug Administration ( Arthur W. Nienhuis, MD )
Study ID Numbers:	EPSTRV
Study First Received:	April 28, 2008
Last Updated:	October 1, 2008
ClinicalTrials.gov Identifier:	NCT00669305
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Anemia

Anemia, Hemolytic
Hemoglobinopathy
Thalassemia
Anemia, Sickle Cell
Sickle cell anemia

ClinicalTrials.gov processed this record on January 16, 2009