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
Condition: Adenosine Deaminase Deficiency; ADA-SCID
Study type: Interventional
Phase: Phase 1

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 description: 
      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.
    

Intervention name(s): Lentiviral Gene Transfer
Intervention type(s): Genetic
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Adenosine Deaminase Deficiency; Gene Therapy; Lentiviral Vectors