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

NCT03311503 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: P00023098
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

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

Conditions

Severe Combined Immunodeficiency, X Linked; Gene Therapy

Keywords

lentiviral; Gene therapy; busulfan

Outcome Measures

Primary Outcomes (2)

• The primary objective is to measure event free survival

  Events will include death, infusion of unmanipulated back-up product for failure of hematopoietic recovery, and allogeneic transplant performed for poor immune reconstitution

  1 year post infusion

• T cell reconstitution

  * CD3+ T cell count ≥300 cells/microliter in peripheral blood * Gene marking ≥0.1 copies/cell in sorted CD3+ T cells

  1 year post infusion

Study Arms (1)

Treatment arm

EXPERIMENTAL

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

Biological: autologous CD34+ cell transduced with G2SCID vector

Interventions

autologous CD34+ cell transduced with G2SCID vector BIOLOGICAL

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

Treatment arm

Eligibility Criteria

• Age: 0 Years - 5 Years
• Gender Eligibility Details: X linked
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \- 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.
• \. Age at least 8 weeks by the time of busulfan administration

You may not qualify if:

• 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).
• Mechanical ventilation including continuous positive airway pressure
• Abnormal liver function defined by AST and ALT \>10 times the upper range of normal OR Bilirubin \>2 mg/dL
• Shortening fraction on echocardiogram \<25% or ejection fraction \<50%
• Renal failure defined as glomerular filtration rate \<30 ml/min/1.73 m2 or dialysis dependence
• Uncontrolled seizure disorder
• Encephalopathy
• Documented coexistence of any disorder known to affect DNA repair
• Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease
• Patients with evidence of infection with HIV-1
• 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.

Sponsors & Collaborators

• David Williams: lead

Study Sites (4)

Mattel Children's Hospital - UCLA

Los Angeles, California, 90095, United States

RECRUITING

Emory University/Childrens Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Sung-Yun Pai, MD

  National Institutes of Health (NIH)

  STUDY CHAIR

Central Study Contacts

Colleen Dansereau

CONTACT

6179197008; colleen.dansereau@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Hematology Oncology

Model Details: open labeled, multi-center, phase I/II, cohort study

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: October 17, 2017
• Study Start: February 26, 2018
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: December 11, 2025

Record last verified: 2025-12

Locations

US (4)