PHASE I/II CLINICAL TRIAL OF AUTOLOGOUS HEMATOPOIETIC STEM CELL GENE THERAPY FOR RAG1-DEFICIENT SEVERE COMBINED IMMUNODEFICIENCY

Phase 2

Recruiting

Conditions: RAG1 SCID
severe combined immunodeficiency
10021460

Registration Number: NL-OMON54570

Lead Sponsor: eids Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

- RAG1 deficient SCID as confirmed by genetic analysis
- Peripheral blood T cells < 300/µL and/or naïve T cells < 1/µL
- lack of an available HLA-matched donor (i.c. HLA-identical sibling or 10/10
(A, B, C, DR, DQ) allele-matched (un)related donor)
- Age < 2 years
- Age at least 8 weeks by the time of busulfan and fludarabine administration
- Signed consent form (parental or guardian)
- Able to return to the local HSCT centre for follow-up (per protocol) during
the 2-year study and the 15 year long-term off study review

Exclusion Criteria

- availability of a HLA-matched donor (i.c. HLA-identical sibling or 10/10 (A,
B, C, DR, DQ) allele-matched (un)related donor)
- RAG 1 deficiency with peripheral blood T cells > 300/µL and/or naïve T cells
> 1/µL
- Previous allogeneic stem cell transplantation
- Significant organ dysfunction/co-morbidity (including but not limited to the
ones listed below)
a. Mechanical ventilation
b. Shortening fraction on echocardiogram <25%
c. Renal failure defined as dialysis dependence
d. Uncontrolled seizure disorder

- Omenn syndrome
- Any other condition that the investigator considers is a contraindication
to collection and/or infusion of transduced 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-ceel Leukemia Virus
(HTLV) infection).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoints are feasibility based on the successful generation of an<br /><br>IMP meeting the release criteria for administration to RAG1 deficient SCID<br /><br>patients, and safety based on event free survival (EFS) after infusion of the<br /><br>IMP with events defined as a) infusion of unmanipulated backup stem cell<br /><br>product and/or allogeneic HSCT because of failure of hematological and/or<br /><br>immunological reconstitution after RAG1 LV cell infusion and b) occurrence of<br /><br>insertional mutagenesis presenting as malignant disease.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are a) overall survival, b) efficacy by determining T cell<br /><br>reconstitution (CD3 T cells > 300/µL blood), thymic function (presence of naïve<br /><br>CD4 T cells) and T and B cell receptor molecular repertoire at one year and<br /><br>immunoglobulin substitution dependence at two years after infusion of the RAG1<br /><br>LV CD34+ cells, and vector copy numbers in leukocyte subpopulations at one<br /><br>year, and c) clinical outcome by determining the rate of infections, recovery<br /><br>from failure to thrive, and quality of life.</p><br>