This trial is active, not recruiting.

Condition immunologic deficiency syndromes
Treatment gene transduced cd34+ cells
Phase phase 2
Sponsor GlaxoSmithKline
Start date October 2002
End date July 2011
Trial size 18 participants
Trial identifier NCT00598481, 115611, 15386-PRE21


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan
gene transduced cd34+ cells Gene therapy
infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan

Primary Outcomes

time frame: minimum of 1 year

Secondary Outcomes

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

Eligibility Criteria

Male or female participants up to 17 years old.

Inclusion Criteria: - ADA-SCID with no HLA-identical sibling donor - pediatric age and at least one of the following criteria: - inadequate immune response after PEG-ADA for > 6 months - patients who discontinued PEG-ADA due to intolerance, allergy or auto-immunity - patients for whom enzyme replacement therapy is not a life long therapeutic option Long term follow-up - Patients who have received treatment with the Medicinal Product, either as part of the main clinical study, or previous pilot studies or compassionate use program Exclusion Criteria: - HIV infection - history or current malignancy - Patients who received a previous gene therapy treatment in the 12 months prior to receiving GSK2696273 - any other conditions dangerous for the patients according to the investigator

Additional Information

Official title ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
Description 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
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.