Clinical Trial: Treatment of SCID Due to ADA Deficiency With Autologous Transplantation of Cord Blood or Hematopoietic CD 34+ Cells After Addition of a Normal Human ADA cDNA by the EFS-ADA Lentiviral Vector

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of SCID Due to ADA Deficiency With Autologous Transplantation of Cord Blood or Hematopoietic CD 34+ Cells After Addition of a Normal Human ADA cDNA by the EFS-AD

Brief Summary: This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA under the control of the elongation factor alpha short promoter (EFS). In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate in the study. To increase engraftment and selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent. Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow, peripheral blood or cord blood, exposed to lentiviral vector-mediated gene transfer and re-infused into the patient through a peripheral vein. Clinical, immunological and molecular follow-up studies will assess safety, toxicity, and efficacy of the procedure.

Detailed Summary: This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of the EFS-ADA lentiviral vector to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. The EFS-ADA vector expresses the human ADA cDNA under the control of the elongation factor alpha short promoter (EFS). In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate in the study. To increase engraftment and selected advantage or gene-corrected cells, busulfan will be used as a cytoreductive agent. Enzyme replacement (PEG-ADA) will be discontinued 30 days after infusion of gene-corrected cells. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow, peripheral blood or cord blood, exposed to lentiviral vector-mediated gene transfer and re-infused into the patient through a peripheral vein. Clinical, immunological and molecular follow-up studies will assess safety, toxicity, and efficacy of the procedure.
Sponsor: National Human Genome Research Institute (NHGRI)

Current Primary Outcome: To examine the safety of autologous transplantation of hematopoietic CD34+ cells transduced with the EFS-ADA lentiviral vector after non-myeloablative conditioning with busulfan and while withholding of PEG-ADA enzyme replacement therapy@@... [ Time Frame: 3 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: December 20, 2013
Date Started: December 16, 2013
Date Completion:
Last Updated: May 12, 2017
Last Verified: March 6, 2017