Gene therapy for X-linked severe combined immunodeficiency

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

This study is testing a new gene therapy for young children with X-linked severe combined immunodeficiency to see if it can help restore their immune system when they don't have a matching donor for a stem cell transplant.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 8 Weeks to 5 Years
• Sex: Male
• Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (London, Greater London)
• Trial ID: NCT03601286 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of lentiviral gene therapy to treat X-linked severe combined immunodeficiency (SCID-X1), a genetic disorder that severely impairs the immune system. The approach involves transducing the patient's CD34+ cells with a lentiviral vector to restore normal immune function. Eligible participants are children under 5 years old who lack a matched donor for traditional stem cell transplantation. The trial aims to provide a long-term solution for patients who cannot receive standard treatments.

Who should consider this trial

Good fit: Ideal candidates are children under 5 years old diagnosed with SCID-X1 and lacking a matched related donor.

Not a fit: Patients with active, therapy-resistant infections may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could significantly improve immune function and quality of life for children with SCID-X1.

How similar studies have performed: Other studies using gene therapy for SCID have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. 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
2. Lack of an HLA identical (A, B, C, DR, DQ) related donor
3. Age \<5 years
4. Signed informed consent
5. Documentation of willingness to follow up for 15 years post-infusion
6. If the patient has previously undergone allogeneic transplant or gene therapy, insufficiency of graft-derived T cell engraftment must be documented.
7. Age at least 8 weeks of age by the time of busulfan administration

Exclusion Criteria:

1. 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).

   1. Mechanical ventilation including continuous positive airway pressure
   2. Abnormal liver function defined by AST and ALT \>10 times the upper range of normal OR Bilirubin \>2 mg/dL
   3. Shortening fraction on echocardiogram \<25% or ejection fraction \<50%
   4. Renal failure defined as glomerular filtration rate \<30 ml/min/1.73 m2 or dialysis dependence
2. Uncontrolled seizure disorder
3. Encephalopathy
4. Documented coexistence of any disorder known to affect DNA repair
5. Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease
6. Patients with evidence of infection with HIV-1
7. Previous allogeneic transplant with cytoreductive chemotherapy
8. Major (life-threatening) congenital anomalies. Examples of "major (life-threatening) congenital anomalies" include, but are not limited to: unrepaired cyanotic heart disease, hypoplastic lungs, anencephaly or other major central nervous system malformations, other severe non-repairable malformations of the gastrointestinal or genitourinary tracts that significantly impair organ function.
9. Other conditions which in the opinion of the P.I. or Co-investigators, contra-indicate collection and/or infusion of transduced cells or indicate patient's inability to follow the protocol. These may include for example clinical ineligibility to receive anaesthesia, severe deterioration of clinical condition of the patient after collection of bone marrow but before infusion of transduced cells, or documented refusal or inability of the family to return for scheduled visits. There may be other unforeseen rare circumstances that would result in exclusion of the patient, such as sudden loss of legal guardianship.

Where this trial is running

London, Greater London

• Great Ormond Street Hospital for Children NHS Foundation Trust — London, Greater London, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Claire Booth, Dr — UCL Great Ormond Street Institute of Child Health
• Study coordinator: Claire Booth, Dr

Conditions: Severe Combined Immunodeficiency, X-Linked