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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT03311503
• Date of registration: 12/10/2017
• Prospective Registration: Yes
• Primary sponsor: David Williams
• Public title: Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning
• Scientific title: Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning
• Date of first enrolment: January 19, 2018
• Target sample size: 12
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03311503
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom, United States

Contacts

• Name: Sung-Yun Pai, MD
• Affiliation: National Institutes of Health (NIH)

Key inclusion & exclusion 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 old or younger 4. Signed informed consent 5. Documentation of willingness to follow
up for 15 years post-infusion as currently required by the FDA 6. If the patient has
previously undergone allogeneic transplant, lack of donor T cell engraftment must be
documented.

7. Age at least 8 weeks 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. 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.

8. 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
anesthesia, severe deterioriation 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

-



Age minimum: N/A
Age maximum: 5 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Gene Therapy

Severe Combined Immunodeficiency, X Linked

Intervention(s)

Biological: autologous CD34+ cell transduced with G2SCID vector

Primary Outcome(s)

The primary objective is to measure event free survival [Time Frame: 1 year post infusion]

T cell reconstitution [Time Frame: 1 year post infusion]

Secondary ID(s)

P00023098

Source(s) of Monetary Support

Please refer to primary and secondary sponsors