Phase I/II Clinical Trial Stem Cell Gene Therapy in RAG1-Deficient SCID

Plain-language summary

This study examines a gene therapy in infants with RAG1-deficient SCID (severe combined immunodeficiency). It is open to infants under 2 years of age who have genetically confirmed RAG1-deficient SCID and who do not have a suitable HLA-matched donor. It is a non-phased study and is currently recruiting participants.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Not Applicable

Status

Recruiting

Sponsor

Leiden University Medical Center

Intervention

Gene therapy

Start date

7/23/2021

Estimated completion

12/31/2029

Countries

Australia, Italy, Netherlands, Poland, Spain, Turkey (Türkiye), United Kingdom

Related genes

Locations

• Melbourne, Australia
• Roma, Italy
• Leiden, Netherlands
• Wroclaw, Poland
• Barcelona, Spain
• Kayseri, Turkey (Türkiye)
• London, United Kingdom

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. RAG1-deficient SCID as confirmed by genetic analysis
2. Peripheral blood T cells \< 300/μL and/or naïve T cells \< 1/μL
3. Age \< 2 years
4. Age at least 8 weeks by the time of busulfan and fludarabine administration
5. Lack of an available HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
6. Signed informed consent (parental or guardian)
7. 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 Criteria:

1. Availability of an HLA-matched donor (HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor)
2. RAG1 deficiency with peripheral blood T cells \> 300/μL and/or naïve T cells \> 1/μL
3. Omenn syndrome
4. Previous allogeneic HSCT
5. Significant organ dysfunction/co-morbidity (including but not limited to the ones listed below):

   1. Mechanical ventilation
   2. Shortening fraction on echocardiogram \<25%
   3. Renal failure defined as dialysis dependence
   4. Uncontrolled seizure disorder
6. 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.
7. Human immunodeficiency virus (HIV) infection or Human T-cell Leukemia Virus (HTLV) infection