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Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency

This study is currently recruiting participants.
Verified September 2015 by Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor:
ClinicalTrials.gov Identifier:
NCT01380990
First Posted: June 27, 2011
Last Update Posted: September 14, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Great Ormond Street Hospital for Children NHS Foundation Trust
June 23, 2011
June 27, 2011
September 14, 2015
November 2012
December 2018   (Final data collection date for primary outcome measure)
Overall survival following gene therapy [ Time Frame: 3 years follow up ]
Same as current
Complete list of historical versions of study NCT01380990 on ClinicalTrials.gov Archive Site
  • Reduction in frequency of infections [ Time Frame: evaluated from 1st year after treatment by clinical history, complete physical examinations, haematological and microbiological tests ]
  • Long term immune reconstitution as assessed by sustained improvement in thymic function [ Time Frame: 3 years follow up ]
Same as current
Not Provided
Not Provided
 
Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency
Phase I/II, Non-controlled, Open-label, Non-randomised, Single-centre Trial to Assess the Safety and Efficacy of EF1αS-ADA Lentiviral Vector Mediated Gene Modification of Autologous CD34+ Cells From ADA-deficient Individuals

Adenosine Deaminase (ADA) is an enzyme, needed by body to develop lymphocytes of the immune system. Children who are born in mutations with mutations in ADA gene have severe combined immunodeficiency (SCID). Children with ADA-deficient SCID generally die in the first year of life from severe infections because they do not have immune system that can fight against infections. ADA deficient individuals can be cured by bone marrow transplant, but the best results are obtained when there is fully matched family donor is available. In the absence of a matched related donor, transplants from unrelated or mismatched donors have a much worse outcome. There is a form of enzyme therapy (PEG-ADA) for ADA-deficient SCID, in which children receive injections of purified ADA enzyme 1-2 times each week. These injections can allow the immune system to recover to a level that protects children from infections.

However, these injections have to be given weekly and are very expensive (£ 125,000 - 200,000 annually) and the recovery of the immune system is not sustained over time.

Gene therapy for ADA-deficient SCID could be performed by introducing a normal copy of the human ADA gene into the blood forming stem cells of the patient's bone marrow by using a new type of gene delivery system (in this trial called a lentiviral vector). The gene corrected cells are then transplanted back into the patient after small dose of chemotherapy. These gene corrected stem cells can survive into the body and make lymphocytes. In this trial, we will determine whether gene therapy for ADA-deficient SCID using lentiviral vector is safe, feasible and effective

Not Provided
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adenosine Deaminase Deficiency
  • Severe Combined Immunodeficiencies (SCID)
Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
EF1αS-ADA lentiviral vector transduced patient Cd34+ cells will be infused in a volume of ~10-20 mls/kg intravenously over 30-45 minutes.
Experimental: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
Intervention: Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10
December 2018
December 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of ADA-SCID confirmed by DNA sequencing or by confirmed absence of <3% of ADA enzymatic activity in peripheral blood (or for neonates) umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy
  • Patients who lack a fully HLA-matched family donor
  • Patients < 5 years of age
  • Parental/guardian signed informed consent

Exclusion Criteria:

  • Patients who have a fully HLA-matched family donor
  • Patients > 5 years of age
  • Cytogenetic abnormalities on peripheral blood
  • Evidence of infection with HIV-1&2, hepatitis B, HCV
  • Evidence of active malignant disease
  • Known sensitivity to busulfan
Sexes Eligible for Study: Male
up to 5 Years   (Child)
No
Contact: Bobby Gaspar, Professor +44 (0)207 905 2319 H.Gaspar@ucl.ac.uk
United Kingdom
 
 
NCT01380990
10-MI-29
No
Not Provided
Not Provided
Great Ormond Street Hospital for Children NHS Foundation Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Not Provided
Principal Investigator: Bobby Gaspar, Professor Great Ormond Street Hospital for Children NHS Foundation Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP