RecruitingPhase 1

Lentiviral Gene Therapy for X-linked Severe Combined Immunodeficiency

United Kingdom5 participantsStarted 2018-12-21

Plain-language 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

Who can participate

Age range8 Weeks – 5 Years

SexMALE

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 SCID-X1 based on immunophenotype and lack of T cell function (proliferation to PHA \<10% of the lower limit of normal for the laboratory) AND confirmed by a mutation in IL2RG
✓. Lack of an HLA identical (A, B, C, DR, DQ) related donor
✓. Age \<5 years
✓. Signed informed consent
✓. Documentation of willingness to follow up for 15 years post-infusion
✓. If the patient has previously undergone allogeneic transplant or gene therapy, insufficiency of graft-derived T cell engraftment must be documented.
✓. Age at least 8 weeks of age by the time of busulfan administration

Exclusion criteria

✕. Patients with an active, therapy-resistant infection. Infections that are known to be highly morbid in SCID patients will be considered active and therapy-resistant if the infectious agent is repeatedly isolated despite a minimum of 2 weeks of appropriate therapy and is associated with significant organ dysfunction (including but not limited to abnormalities listed below).

What they're measuring

Measure event-free survival after 1 year after gene transfer

Timeframe: 1 year

Measure T cell immune reconstitution: CD3+ T cell count

Timeframe: 1 year

Measure T cell immune reconstitution; gene marking

Timeframe: 1 year

Trial details

NCT IDNCT03601286

SponsorGreat Ormond Street Hospital for Children NHS Foundation Trust

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-08

Contact for this trial

Claire Booth, Dr

0207 905 2198 c.booth@ucl.ac.uk

View on ClinicalTrials.gov More Severe Combined Immunodeficiency, X-Linked trials

Plain-language summary

Who can participate

Age range8 Weeks – 5 Years

SexMALE

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 SCID-X1 based on immunophenotype and lack of T cell function (proliferation to PHA \<10% of the lower limit of normal for the laboratory) AND confirmed by a mutation in IL2RG
✓. Lack of an HLA identical (A, B, C, DR, DQ) related donor
✓. Age \<5 years
✓. Signed informed consent
✓. Documentation of willingness to follow up for 15 years post-infusion
✓. If the patient has previously undergone allogeneic transplant or gene therapy, insufficiency of graft-derived T cell engraftment must be documented.
✓. Age at least 8 weeks of age by the time of busulfan administration

Exclusion criteria

✕. Patients with an active, therapy-resistant infection. Infections that are known to be highly morbid in SCID patients will be considered active and therapy-resistant if the infectious agent is repeatedly isolated despite a minimum of 2 weeks of appropriate therapy and is associated with significant organ dysfunction (including but not limited to abnormalities listed below).