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

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Brief Title

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

Official Title

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

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 and
      UCLA Mattel Children's Hospital. Patients will receive transduced cells after low dose
      targeted busulfan pre-conditioning (n=10).

      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

      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

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

The primary objective is to measure event free survival


Severe Combined Immunodeficiency, X Linked


autologous CD34+ cell transduced with G2SCID vector

Study Arms / Comparison Groups

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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 19, 2018

Completion Date

January 1, 2024

Primary Completion Date

January 1, 2022

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

        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

          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





N/A - 5 Years

Accepts Healthy Volunteers



Sung-Yun Pai, MD, 6179197008, [email protected]

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

David Williams

Study Sponsor

Sung-Yun Pai, MD, Study Chair, National Institutes of Health (NIH)

Verification Date

April 2021