Clinical Trial: ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
Brief Summary: This is a phase I/II protocol to evaluate the safety and efficacy of ADA gene transfer into hematopoietic stem/progenitor cells for the treatment of adenosine deaminase (ADA)-deficiency. This condition is an autosomal recessive form of Severe Combined Immunodeficiency (SCID) characterized by impaired immune responses, recurrent infections, failure to thrive and systemic toxicity due to accumulation of purine metabolites. Transplants from an HLA-identical sibling donor is the treatment of choice, but available for a minority of patients. The use of alternative bone marrow donors or enzyme replacement therapy is associated with important drawbacks. The drug product studied in this protocol consists of autologous CD34+ hematopoietic stem/progenitor cells engineered ex vivo with a retroviral vector encoding the therapeutic gene ADA. The engineered CD34+ cells are infused following a nonmyeloablative conditioning with busulfan to make space in the bone marrow. The study objectives are: a) to evaluate the safety and the clinical efficacy of gene therapy, in the absence of enzyme replacement therapy; b) to evaluate the biological activity (engraftment, ADA expression) of ADA transduced CD34+ cells and their hematopoietic progeny. c) to evaluate the immunological reconstitution and purine metabolism after gene therapy.
Detailed Summary:
The safety of the study will be evaluated by description of all adverse events and adverse drug reactions.
The study is aimed at reaching the minimum sample size of ten patients.
Long term follow up all patients enrolled into the study will have a long term follow period from 4 to 8 years after gene therapy
Sponsor: GlaxoSmithKline
Current Primary Outcome: survival [ Time Frame: minimum of 1 year ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Change in the rate of severe infection [ Time Frame: During follow up ]
- T-lymphocyte counts [ Time Frame: one year ]
- Modification of the systemic metabolic defect [ Time Frame: one year ]
- presence of genetically modified cells in the BM and PB [ Time Frame: one year ]
Original Secondary Outcome: Same as current
Information By: GlaxoSmithKline
Dates:
Date Received: January 10, 2008
Date Started: October 2002
Date Completion: June 2019
Last Updated: April 21, 2016
Last Verified: April 2016
