Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency

Plain-language summary

This study evaluates a gene therapy (delivering the ADA gene into the patient's own CD34+ stem cells via a lentiviral vector) in patients with Severe Combined Immunodeficiency caused by ADA enzyme deficiency (ADA-SCID). It included children (mostly under 5) with DNA-confirmed ADA-SCID and no fully HLA-matched family donor. It was a Phase 1/Phase 2 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Intervention

Infusion of autologous EFS-ADA LV CD34+ cells, Haematopoietic Stem Cell Transplantation (HSCT), Busulfan, Peg-Ada

Start date

11/15/2012

Estimated completion

12/23/2019

Countries

United Kingdom

Related genes

Locations

• London, United Kingdom

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Gene Therapy (On Trial)

Inclusion Criteria:

1. 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
2. Patients who lack a fully Human leukocyte antigen (HLA)-matched family donor
3. 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)
4. Parental/guardian signed informed consent

Exclusion Criteria:

1. Cytogenetic abnormalities on peripheral blood
2. Evidence of active malignant disease
3. Known sensitivity to busulfan
4. If applicable, confirmed pregnancy (to be tested in patients above 12 years old)

Gene Therapy (CUP)

A group of patients were treated under CUP (GOSH special license) either because the study was not yet open and patients needed urgent treatment, or because they were outside of the inclusion/exclusion criteria or received Investigational Medicinal Product (IMP) followed a different process (ie, received in two infusions). Patients followed the same protocol steps and study visits.

Historical Control Group

Inclusion Criteria:

1. 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
2. Patients (male or female) between 0-18 years at time of treatment
3. Patient treated with allogeneic haematopoietic stem cell transplantation since 2000