Lentiviral gene therapy for SCID-X1
Research type
Research Study
Full title
Phase I/II study of lentiviral gene transfer for SCID-X1 with low dose targeted busulfan
IRAS ID
236627
Contact name
Claire Booth
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children NHS Trust
Eudract number
2018-000673-68
Duration of Study in the UK
5 years, 0 months, 2 days
Research summary
X-linked severe combined immunodeficiency (SCID-X1) is a genetic disorder that affects boys. It is caused by errors in a gene that is critical in making the immune system work. The basic defect lies in the development and function of cells of the immune system known as lymphocytes. These are crucial for protection against infection. Common infections, which have little effect on normal individuals, can therefore have severe consequences in SCID-X1. Although some protection can be provided by drugs such as antibiotics and antibodies, this disease is usually fatal within the first few years of life. Bone marrow transplant is the standard treatment for patients with SCID-X1 and the survival rates for patients are very good (80-90%) when a fully matched family or unrelated donor is available. However if such a donor is not available the risks and chance for complication are higher. The reasons for this relate to the toxic effect of the chemotherapy treatment required to prepare the patient for transplant (which is not required if the marrow is well matched), and also to graft versus host disease (GvHD), a process where lymphocytes from the donor recognise the recipient and attack body tissues. For those patients without a fully matched donor, alternative treatments that have fewer side effects are highly desirable. An alternative option to bone marrow transplant is gene therapy where the aim is to deliver a normal copy of the gene that has been identified as mutated and therefore responsible for a patient's SCID. Previous clinical trials have utilised a gammaretroviral vector to deliver a normal copy of the gene to the patient however despite the majority of patients experiencing a reconstitution of their immune system these vectors are associated with insertational oncogenesis which has led to some patients developing leuakeamia following treatment with gene therapy.
In this trial, an ex-vivo lentiviral vector based gene therapy will be assessed in SCID-X1 patients. The vector construct in ex-vivo lentiviral gene therapy incorporates safety features that make it less prone to insertional oncogenesis. Patients will also receive low dose targeted pre-gene therapy conditioning with a stem call active agent, busulfan, which we think will promote pluripotent HSC engraftment and thereby generation of gene marked B cells and humoral immune reconstitution.REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/1309
Date of REC Opinion
9 Oct 2018
REC opinion
Further Information Favourable Opinion