Lentiviral Gene Therapy for X-linked Severe Combined Immunodeficiency
Status:
Recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
Summary
Severe combined immunodeficiency disorder (SCID) is a heterogeneous group of inherited
disorders characterized by a profound reduction or absence of T lymphocyte function,
resulting in lack of both cellular and humoral immunity. SCID arises from a variety of
molecular defects which affect lymphocyte development and function. The most common form of
SCID is an X-linked form (SCID-X1), which accounts for 30-50% of all cases. SCID-X1 is caused
by defects in the common cytokine receptor gamma chain, which was originally identified as a
component of the high affinity interleukin-2 receptor (IL2RG).
Allogeneic haematopoietic stem cell transplantation (HSCT), which replaces the patient's bone
marrow with that of a healthy donor, is the only treatment that definitively restores the
normal function of the bone marrow. HSCT is the first choice of treatment for patients with
signs of bone marrow failure and a fully-matched related donor. However, patients without a
fully-matched related donor have much worse overall outcomes from HSCT.
This study will investigate whether patients with SCID-X1 without a fully matched related
donor may benefit from gene therapy. To do this the investigators propose to perform a phase
I/II clinical trial to evaluate the safety and efficacy (effect) of gene therapy for SCID-X1
patients using a lentivirus delivery system containing the IL2RG gene. Up to 5 eligible
SCID-X1 patients will undergo mobilisation and harvest of their haematopoietic stem precursor
cells (HPSCs). In the laboratory the disabled lentivirus will be used to insert a normal
human IL2RG gene into the patient's harvested HPSCs. Patients will receive chemotherapy
conditioning prior to cell infusion, in order to enhance grafting. The genetically corrected
stem cells will then be re-infused into the patient. Patients will be followed up for 2
years. This trial will determine whether gene therapy for SCID-X1 using a lentiviral vector
is safe, feasible and effective
Phase:
Phase 1
Details
Lead Sponsor:
Great Ormond Street Hospital for Children NHS Foundation Trust