Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency
United Kingdom36 participantsStarted 2012-11-15
Plain-language summary
This is a historically controlled, non-randomized Phase I/II clinical trial to assess the safety and efficacy of autologous transplantation of CD34+ hematopoietic stem/progenitor cells (HSPCs), obtained from infants affected by ADA-SCID, following transduction of the HSPCs with a lentiviral vector (LV) carrying the human ADA complementary DNA (cDNA) under the control of the elongation factor 1 alpha shortened (EFS) promoter. Subjects treated in the trial receive the infusion of autologous, transduced cells following marrow cytoreduction with busulfan. The outcomes are compared to those observed in a historical control group of patients who received an allogeneic hematopoietic stem cell transplant (HSCT).
This Phase I/II clinical trial will be performed at Great Ormond Street Hospital (GOSH), London, United Kingdom.
Who can participate
Age range
15 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
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) in umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of Polyethylene glycol-modified ADA (PEG-ADA) replacement therapy
. Patients who lack a fully Human leukocyte antigen (HLA)-matched family donor
. Patients (male or female) \<5 years of age OR Patients (male or female) ≥ 5 years to 15 years of age who have preserved thymic function as evidenced by presence of \>10 % naïve T cells (CD4+45RA+27+ cells)
. Parental/guardian signed informed consent
Exclusion criteria
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Timeframe: 12 months
2
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)
Timeframe: 12 months
3
Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils)
Timeframe: 36 months
4
VCN in Peripheral Blood Mononuclear Cells (PBMCs)
Timeframe: 36 months
5
VCN in CD3+ T Cells
Timeframe: 36 months
6
VCN in CD19+ B Cells
Timeframe: 36 months
7
Change From Baseline in CD3+ T Cell Counts (1 Year)
Timeframe: 12 months
8
Trial details
NCT IDNCT01380990
SponsorGreat Ormond Street Hospital for Children NHS Foundation Trust
. If applicable, confirmed pregnancy (to be tested in patients above 12 years old)
. Diagnosis of ADA-SCID confirmed by DNA sequencing OR by confirmed absence of \<3% of ADA enzymatic activity in peripheral blood or (for neonates) in umbilical cord blood erythrocytes and/or leucocytes or in cultured foetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy
. Patients (male or female) between 0-18 years at time of treatment
. Patient treated with allogeneic haematopoietic stem cell transplantation since 2000
Change From Baseline in CD3+ T Cell Counts (3 Years)
Timeframe: 36 months
9
ADA Activity in Erythrocytes
Timeframe: 36 months
10
Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes
Timeframe: 36 months
11
Frequency of Vector Integration Into Known Protooncogenes (3 Years)