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 range15 Years
SexALL
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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
✕. Cytogenetic abnormalities on peripheral blood
✕. Evidence of active malignant disease
✕. Known sensitivity to busulfan
✕. If applicable, confirmed pregnancy (to be tested in patients above 12 years old)
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
Change From Baseline in CD3+ T Cell Counts (3 Years)
Timeframe: 36 months
9
Trial details
NCT IDNCT01380990
SponsorGreat Ormond Street Hospital for Children NHS Foundation Trust
. 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
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)