Phase I/II Clinical Trial Stem Cell Gene Therapy in RAG1-Deficient SCID
Phase I/II Clinical Trial of Autologous Hematopoietic Stem Cell Gene Therapy in RAG1-Deficient Severe Combined Immunodeficiency
Leiden University Medical Center
10 participants
Jul 23, 2021
INTERVENTIONAL
Conditions
Summary
This study is a prospective, non-randomized, open-label, two-centre phase I/II intervention study designed to treat children up to 24 months of age with RAG1-deficient SCID with an indication for allogeneic hematopoietic stem cell transplantation but lacking an HLA-matched donor. The study involves infusion of autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (hereafter called RAG1 LV CD34+ cells) in five patients with RAG1-deficient SCID.
Eligibility
Inclusion Criteria7
- RAG1-deficient SCID as confirmed by genetic analysis
- Peripheral blood T cells < 300/μL and/or naïve T cells < 1/μL
- Age < 2 years
- Age at least 8 weeks by the time of busulfan and fludarabine administration
- Lack of an available HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
- Signed informed consent (parental or guardian)
- Able to return to the study centre for follow-up (per protocol) during the 2-year study and the 15-year long-term off study review
Exclusion Criteria11
- Availability of an HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
- RAG1 deficiency with peripheral blood T cells > 300/μL and/or naïve T cells > 1/μL
- Omenn syndrome
- Previous allogeneic HSCT
- Significant organ dysfunction/co-morbidity (including but not limited to the ones listed below):
- Mechanical ventilation
- Shortening fraction on echocardiogram <25%
- Renal failure defined as dialysis dependence
- Uncontrolled seizure disorder
- Any other condition that the investigator considers is a contraindication to collection and/or infusion of trans-duced cells for that individual or indicate patient's inability to follow the protocol, for example contraindication f to busulfan, major congenital abnormalities, ineligible to receive anaesthesia, or documented refusal or inability of the family to return for scheduled visits.
- Human immunodeficiency virus (HIV) infection or Human T-cell Leukemia Virus (HTLV) infection
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Interventions
Patients will be infused with autologous CD34+ cells transduced with the pCCL.MND.coRAG1.wpre lentiviral vector (RAG1 LV CD34+ cells).
Locations(7)
View Full Details on ClinicalTrials.gov
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NCT04797260