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

NCT ID: NCT03311503

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-26
• Study Completion Date: 2028-01-01

Brief Summary

This is a phase I/II open label multi-center study in which patients will receive low dose targeted busulfan followed by infusion of autologous CD34+ selected bone marrow or mobilized peripheral blood cells transduced with the G2SCID vector. Subjects will be enrolled over 3 years and be followed for 2 years post-infusion on this protocol, then followed long-term on a separate long-term follow-up protocol.

Enrollment of subjects will be agreed upon by representatives of both sites. Data will be collected uniformly from both sites through an electronic capture system and key laboratory studies will be centralized.

Harvest, cellular manufacturing and infusion will occur at each site using the same SOPs. Key aspects of cellular product characterization will be centralized

Detailed Description

This is an open labeled, multi-center, phase I/II, cohort study involving a single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID in up to 10 patients with X-linked SCID (SCID-X1) at Boston Children's Hospital, UCLA Mattel Children's Hospital, Cincinnatti Childrens Hospital Medical Center, Children's Healthcare of Atlanta. Patients will receive transduced cells after low dose targeted busulfan pre-conditioning (n=12).

Enrolled subjects will be followed for 2 years after infusion on this protocol. Required long-term monitoring for a total of 15 years after infusion will be performed on a separate protocol.

Single infusion of autologous CD34+ cells transduced with the SIN lentiviral vector rHIV_IL2RGcoG2SCID (hereafter G2SCID) The primary objective is to measure event free survival and T cell immune reconstitution at 1 year post-infusion

Secondary objectives are to measure overall survival, event-free survival, safety related to the procedure, and clinical and laboratory measures of efficacy including humoral immune reconstitution and gene marking after gene transfer.

Exploratory objectives include: molecular characterization of gene transfer, detailed assessment of biomarkers of T and B cell development and function, assessment of infections, nutritional status, growth and development post gene therapy, assessment of T cell receptor and B cell receptor repertoire by next generation sequencing, correlation of busulfan levels with immune outcome and molecular measurements of gene transfer

Conditions

Severe Combined Immunodeficiency, X Linked; Gene Therapy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment arm

single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID

Group Type: EXPERIMENTAL

autologous CD34+ cell transduced with G2SCID vector

Intervention Type: BIOLOGICAL

single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID

Interventions

autologous CD34+ cell transduced with G2SCID vector

single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID

Intervention Type: BIOLOGICAL

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 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

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• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 5 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

David Williams

OTHER

Sponsor Role: lead

Responsible Party

David Williams

Chief Hematology Oncology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sung-Yun Pai, MD

Role: STUDY_CHAIR

National Institutes of Health (NIH)

Locations

Mattel Children's Hospital - UCLA

Los Angeles, California, United States

Site Status: RECRUITING

Emory University/Childrens Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status: RECRUITING

Boston Childrens Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Colleen Dansereau

Role: CONTACT

colleen.dansereau@childrens.harvard.edu

6179197008

Facility Contacts

Donald Kohn, MD

Role: primary

(310) 825-6708

Shanmuganathan Chandrakasan, MD

Role: primary

Shanmuganathan.Chandrakasan@emory.edu

404-727-8877

Susan Prockop, MD

Role: primary

Susan.Prockop@childrens.harvard.edu

617-355-3087

Sharat Chandra, M.D.

Role: primary

Sharat.Chandra@cchmc.org

(513) 636-4266

Other Identifiers

P00023098

Identifier Type: -

Identifier Source: org_study_id