Phase I/II Study of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan

Who is this study for? Pediatric male patients age 8 weeks to 5 years with bare lymphocyte syndrome SCID-X1
What treatments are being studied? Lentiviral vector transduced CD34+ cells
Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
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

Eligibility
Participation Requirements
Sex: Male
Minimum Age: 1 month
Maximum Age: 5
Healthy Volunteers: f
View:

• 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

Locations
Other Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
RECRUITING
London
Contact Information
Primary
Claire Booth, Dr
c.booth@ucl.ac.uk
0207 905 2198
Backup
Karen Oprych, Dr
k.gladwin@ucl.ac.uk
Time Frame
Start Date: 2018-12-21
Estimated Completion Date: 2026-08
Participants
Target number of participants: 5
Treatments
Experimental: Lentiviral vector transduced CD34+ cells
Single arm, non-randomised cohort of up to 5 patients with X-linked Severe Combined Immunodeficiency. CD34+ cells will be collected via bone marrow harvest or leukapheresis. The collected cells will then be purified, cultured and transduced with the G2SCID lentiviral vector. Transduced cells will be frozen. A minimum of 2.5 x 106/kg CD34+ cells after transduction with a minimum transduction efficiency of 0.7 copies/cell is required for infusion into the patient. The patient will receive non-myeloablative conditioning with intravenous busulfan the two or three days prior to cell infusion. The frozen cells will be thawed on the day of infusion and the cells administered according to hospital procedures. The patient will remain in hospital until sufficient cover of the patient's immune system
Sponsors
Leads: Great Ormond Street Hospital for Children NHS Foundation Trust

This content was sourced from clinicaltrials.gov

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