Severe Combined Immunodeficiency, X LinkedPhase 1/2NCT03311503
Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning
A Phase 1/2 study testing autologous CD34+ cell transduced with G2SCID vector in people with Severe Combined Immunodeficiency, X Linked and Gene Therapy, run by David Williams at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 5 years, men only
- Conditions the study is for
- Severe Combined Immunodeficiency, X Linked, Gene Therapy
- What is being tested?
- autologous CD34+ cell transduced with G2SCID vector
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 4 sitesUnited States
- Study dates
- 26 Feb 2018to 1 Jan 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 5 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.
- 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
- -
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Emory University/Childrens Healthcare of Atlanta
Atlanta, Georgia, 30322
Shanmuganathan Chandrakasan, MD, 404-727-8877, Shanmuganathan.Chandrakasan@emory.edu
Shanmuganathan Chandrakasan, MD
- Recruiting
Boston Childrens Hospital
Boston, Massachusetts, 02115
Susan Prockop, MD, 617-355-3087, Susan.Prockop@childrens.harvard.edu
Susan Prockop, MD
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Sharat Chandra, M.D., (513) 636-4266, Sharat.Chandra@cchmc.org
Sharat Chandra, M.D.
- Recruiting
Mattel Children's Hospital - UCLA
Los Angeles, California, 90095
Donald Kohn, MD, (310) 825-6708
About this study
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
Read the 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
- Being tested
- autologous CD34+ cell transduced with G2SCID vector
- Keywords
- lentiviral, Gene therapy, busulfan
- Medical subject headings
- X-Linked Combined Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous CD34+ cell transduced with G2SCID vectorBiological
single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID Receives: Biological: autologous CD34+ cell transduced with G2SCID vector |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 1 year post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2017
- Study start26 Feb 2018
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Combined Immunodeficiency, X LinkedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- open labeled, multi-center, phase I/II, cohort study
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Williams
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Williams, Boston Children's Hospital
- Investigators
- Sung-Yun Pai, MD, Study chair, National Institutes of Health (NIH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03311503
- Sponsor's protocol ID
- P00023098
- Status last verified
- Dec 2025
- First submitted
- 12 Oct 2017
- Last updated
- 11 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning
- ClinicalTrials.gov ID
- NCT03311503
- Acronym / sponsor ID
- P00023098
- Keywords
- lentiviral, Gene therapy, busulfan
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- David WilliamsUniversity, hospital or other
- Study start
- 26 Feb 2018 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 17 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open labeled, multi-center, phase I/II, cohort study
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Biological: autologous CD34+ cell transduced with G2SCID vectorsingle infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID |
Who may qualify
- Ages
- 0 to 5 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (13 listed)
- 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).
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| autologous CD34+ cell transduced with G2SCID vectorsingle infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) lentiviral vector G2SCID | Biological | Treatment arm |
Primary outcome
The primary objective is to measure event free survival
Time frame: 1 year post infusion
Events will include death, infusion of unmanipulated back-up product for failure of hematopoietic recovery, and allogeneic transplant performed for poor immune reconstitution
T cell reconstitution
Time frame: 1 year post infusion
* CD3+ T cell count ≥300 cells/microliter in peripheral blood * Gene marking ≥0.1 copies/cell in sorted CD3+ T cells
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sung-Yun Pai, MD study chair
National Institutes of Health (NIH)
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing autologous CD34+ cell transduced with G2SCID vector in people with Severe Combined Immunodeficiency, X Linked and Gene Therapy, run by David Williams at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Colleen Dansereau (6179197008, colleen.dansereau@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to measure event free survival (time frame: 1 year post infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2025.