Severe Combined Immunodeficiency Disease, X-linkedPhase 1/2LVXSCID-NDNCT01512888

Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants

A Phase 1/2 study testing CL20-i4-EF1α-hγc-OPT, Busulfan and CliniMacs in people with Severe Combined Immunodeficiency Disease, X-linked, run by St. Jude Children's Research Hospital at 3 sites in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record

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Trial summary

Who is it for?: Ages Up to 24 months, men only
Conditions the study is for: Severe Combined Immunodeficiency Disease, X-linked
What is being tested?: CL20-i4-EF1α-hγc-OPT, Busulfan and CliniMacs
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 3 sitesUnited States
Study dates: 17 Aug 2016to Aug 2034
Phase: Phase 1/2
Are there results?: None posted in the registry

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 Up to 24 months
Men only
No healthy volunteers
Child

Who may be able to join

Treatment Eligibility Criteria:
Age <2 years at the time of enrollment.
No prior therapy with allogeneic stem cell transplantation.
A clinical diagnosis of SCID-X1 documented in the medical record.
A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA.
Age > 2 months to < 1 year of age at the time of busulfan administration.

Show all 15Show fewer

Less than 300 CD3+ T-cells by flow cytometry or higher if evidence of maternal engraftment as supported by peripheral blood FISH analysis for XY and XX.
Lymphocyte proliferation to phytohemagglutinin (PHA) <10% of the lower limit of normal for the laboratory.
Treatment Exclusion Criteria:
Availability of a HLA matched sibling for allogeneic transplantation
Prior therapy with allogeneic stem cell transplantation
Positive for HIV infection by genome PCR
Presence of a medical condition indicating that survival will be less than 16 weeks such as the requirement for mechanical ventilation, severe failure of a major organ system, or evidence of a serious, progressive infection that is refractory to medical therapy.
The presence of any medical contraindications to general anesthesia and bone marrow harvest by aspiration
A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care.

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of California-San Francisco
San Francisco, California, 94158
Seattle Children's Research Institute
Seattle, Washington, 98101

Other trials in United States

About this study

Official title: A Pilot Feasibility Study of Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector to Transduce Autologous CD34+ Hematopoietic Cells

SCID-X1 is a genetic disorder of blood cells caused by DNA changes in a gene that is required for the normal development of the human immune system. The purpose of this study is to determine if a new method, called lentiviral gene transfer, can be used to treat SCID-X1. This method involves transferring a normal copy of the common gamma chain gene into the participant's bone marrow stem cells. The investigators want to determine if the procedure is safe, whether it can be done according to the methods they have developed, and whether the procedure will provide a normal immune system for the patient. It is hoped that this type of gene transfer may offer a new way to treat children with SCID-X1 that do not have a brother or sister who can be used as a donor for stem cell transplantation.

Read the detailed description

Bone marrow CD34+ cells will be obtained in the operating room, transduced with the lentiviral vector that contains a normal copy of the γc gene, and reinfused without any myeloreductive conditioning. Participants will be monitored for hematopoietic recovery from busulfan and for severe adverse events for 42 days post gene therapy. The primary endpoint assessing the efficacy of this approach will be T-cell immune reconstitution 52 weeks (± 4) weeks after transplantation. Continued and detailed evaluation of all aspects of immune reconstitution, protocol-related toxicity, and retroviral integration sites will also be performed. This study will evaluate the first use of a SIN lentiviral vector for the treatment of SCID-X1 and may lead to a new form of therapy that could be applied to the majority of newly diagnosed patients.

OBJECTIVES

Assess the safety, feasibility and efficacy of lentiviral gene transfer in newly diagnosed SCID-X1 patients transplanted with autologous CD34+ cells that have been transduced with a self-inactivating lentiviral vector (CL20-i4-EF1α-hγc-OPT) expressing a γc gene.

Primary Objective 1: Evaluate the safety and feasibility of infusing at least 1 million transduced CD34+ cells per kilogram of body weight in SCID-X1 infants.

Primary Objective 2: Evaluate the efficacy of lentiviral gene transfer for inducing significant T-cell reconstitution 52 weeks (± 4 weeks) after transplantation. Significant reconstitution of T cells is defined as at least 2 of the following 3 criteria being present:

The development of T-cell proliferative responses to phytohemagglutinin (PHA) that are ≥ 50% the value seen in normal controls
≥ 1000 autologous CD3+ T-cells/μl in the peripheral blood
≥ 500 autologous CD4+ T-cells/μl in the peripheral blood
≥ 200 autologous CD4+ CD45RA T-cells/μl in the peripheral blood

OTHER PRE-SPECIFIED OBJECTIVES:

Correlate busulfan and its metabolite pharmacokinetics with toxicity, efficacy, engraftment of vector-transduced cells, and event-free survival and overall survival.
Evaluate the efficacy of busulfan dose-targeting with busulfan administration every 24 hours for a total of 2 doses in order to achieve a cumulative busulfan area under the curve of 22 mg*hr/L.
Evaluate B-cell function during longterm follow-up of protocol patients. Evaluation will include γc expression in circulating B-cells, measurement of serum IgG, IgA, and IgM concentration, measurement of antibody responses to vaccination, evaluation of IgG production after cessation of intravenous gamma globulin therapy in patients with clinical indications to discontinue IVIG.
Evaluate NK cell numbers in long term follow-up of protocol patients. Evaluation will include flow cytometry evaluation of NK cell numbers.
Determine the vector copy number and the location of vector-integration sites in sorted blood cells. Sorted T-cells, B-cells, NK cells, granulocytes and monocytes will be evaluated for vector copy number. Vector copy number in sorted T-cells will be evaluated as a potential safety measure and will be reported to the FDA if the vector copy number is greater than 5 copies per T cell in any patient at any time. Studies on sorted cells will also include deep sequencing with an automated sequencer to characterize insertion sites, and expression array analysis of T-cell clones to assay for gene expression alterations within 100 kb of the insertion sites.
Evaluate the overall, long-term safety of lentiviral gene transfer. This will include complete clinical evaluation of any AEs resulting from the gene transfer procedure. If any oncogenic event is seen, this evaluation will include complete molecular characterization of the tumor clone including insertion site analysis, gene expression analysis, and evaluation for the LMO2, Cdkn2a, Notch1, Cyclin D2 gene alterations.

Conditions: Severe Combined Immunodeficiency Disease, X-linked
Being tested: CL20-i4-EF1α-hγc-OPT, Busulfan, CliniMacs
Keywords: SCID, SCID-X1, X-linked SCID, immunodeficiency, gene therapy
Medical subject headings: X-Linked Combined Immunodeficiency Diseases, Immunologic Deficiency Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CL20-i4-EF1α-hγc-OPTGenetic
Also called self inactivating lentiviral vector, IND 14570
Participants will undergo infusion with autologous CD34+ bone marrow cells transduced with a lentiviral vector that contains a normal copy of the human γc gene.
BusulfanDrug
Also called Busulfex®, Myleran®
Given intravenously (IV).
CliniMacsDevice
Isolation and purification of CD34+ stem cells will be done after the unmodified frozen backup is obtained and in accordance with our FDA IND and in accordance with the CliniMacs manual of operations.

Study groups in NCT01512888
Study group	Role	What they receive
Treatment	Experimental	Participants will undergo a bone marrow harvest in the operating room to obtain bone marrow cells. Cells will be isolated and purified utilizing the CliniMacs device. These cells will undergo vector transduction with the lentiviral vector that contains a normal copy of the γc gene gene (CL20-i4-EF1α-hγc-OPT) and then the transduced cells will be reinfused back into the patient. Participants will receive a conditioning regimen of busulfan 3 days prior and 2 days prior to infusion of vector-corrected cells.intervention: CL20-i4-EF1α-hγc-OPT Receives: Genetic: CL20-i4-EF1α-hγc-OPT; Drug: Busulfan; Device: CliniMacs

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of patients with adequate cell collection and processing
The number of patients who underwent no more than two bone marrow harvests and cryopreservation of at least 1.0 million cells/kg following vector transduction.
Measured: Day 0
Number of patients with adequate neutrophil count recovery after busulfan conditioning
Adequate recovery is defined as absolute neutrophil count (ANC) >500 cells/μl by day +42 unless the patient is neutropenic prior to busulfan administration.
Measured: Day 42 post gene transfer
Number of patients without Grade 4 adverse event (AE)
The number of patients experiencing no directly related grade 4 or greater adverse event.
Measured: 42 days post gene transfer
Number of patients with successful reconstitution
Reconstitution with transduced cells defined as detection of vector-marked peripheral blood cells by real time PCR at or above 0.02% VCN in total WBC.
Measured: 42 days post gene transfer
Number of patients with treatment failure
Treatment failure will be defined as lack of adequate cell collection and processing, lack of neutrophil count recovery by day +42, occurrence of grade 4 or greater toxicities by day +42, and/or lack of detection of >0.02% transduced cells in peripheral blood by day +42 post gene transfer.
Measured: 42 days post gene transfer

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Aug 2016Aug 2034

First posted19 Jan 2012 (estimated)
Study start17 Aug 2016
Primary completionAug 2026 (estimated)
Study completionAug 2034 (estimated)

Why it stopped: voluntary hold

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe Combined Immunodeficiency Disease, X-linkedStudies of the same condition, open and under way.
More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01512888
Sponsor's protocol ID: LVXSCID-ND
Other IDs: P01HL053749
Acronym: LVXSCID-ND
Status last verified: Nov 2025
First submitted: 13 Jan 2012
Last updated: 10 Nov 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: Yes

Publications

Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long-Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, Sorrentino BP. Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med. 2019 Apr 18;380(16):1525-1534. doi: 10.1056/NEJMoa1815408.
PubMed 30995372

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
X-linked Severe Combined Immunodeficiency (XSCID)
Not yet recruitingPhase 1/2
SCID-X1 Gene Therapy Via Intravenous Lentiviral (Ivlv-X1) Injection
SCID, X-Linked
RecruitingObservational study
Evaluation of Patients With Immune Function Abnormalities
Chronic Granulomatous Disease (CGD), X-Linked Severe Combined Immune Deficiency (XSCID)
Enrolling by invitationPhase 1/2
Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy
X-linked Severe Combined Immunodeficiency, X-SCID
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome

All Severe Combined Immunodeficiency Disease, X-linked trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Feasibility Study of Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector to Transduce Autologous CD34+ Hematopoietic Cells
ClinicalTrials.gov ID: NCT01512888
Acronym / sponsor ID: LVXSCID-ND / LVXSCID-ND
Conditions: Severe Combined Immunodeficiency Disease, X-linked
Keywords: SCID, SCID-X1, X-linked SCID, immunodeficiency, gene therapy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: SuspendedReason stopped: voluntary hold
Enrolment: 28 participants (estimated)
Lead sponsor: St. Jude Children's Research HospitalUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI), Assisi Foundation, California Institute for Regenerative Medicine (CIRM)
Study start: 17 Aug 2016 (actual)
Primary completion: Aug 2026 (estimated)
Study completion: Aug 2034 (estimated)
First posted: 19 Jan 2012 (estimated)
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.

Detailed description

OBJECTIVES

Primary Objective 1: Evaluate the safety and feasibility of infusing at least 1 million transduced CD34+ cells per kilogram of body weight in SCID-X1 infants.

The development of T-cell proliferative responses to phytohemagglutinin (PHA) that are ≥ 50% the value seen in normal controls
≥ 1000 autologous CD3+ T-cells/μl in the peripheral blood
≥ 500 autologous CD4+ T-cells/μl in the peripheral blood
≥ 200 autologous CD4+ CD45RA T-cells/μl in the peripheral blood

OTHER PRE-SPECIFIED OBJECTIVES:

Correlate busulfan and its metabolite pharmacokinetics with toxicity, efficacy, engraftment of vector-transduced cells, and event-free survival and overall survival.
Evaluate the efficacy of busulfan dose-targeting with busulfan administration every 24 hours for a total of 2 doses in order to achieve a cumulative busulfan area under the curve of 22 mg*hr/L.
Evaluate B-cell function during longterm follow-up of protocol patients. Evaluation will include γc expression in circulating B-cells, measurement of serum IgG, IgA, and IgM concentration, measurement of antibody responses to vaccination, evaluation of IgG production after cessation of intravenous gamma globulin therapy in patients with clinical indications to discontinue IVIG.
Evaluate NK cell numbers in long term follow-up of protocol patients. Evaluation will include flow cytometry evaluation of NK cell numbers.
Determine the vector copy number and the location of vector-integration sites in sorted blood cells. Sorted T-cells, B-cells, NK cells, granulocytes and monocytes will be evaluated for vector copy number. Vector copy number in sorted T-cells will be evaluated as a potential safety measure and will be reported to the FDA if the vector copy number is greater than 5 copies per T cell in any patient at any time. Studies on sorted cells will also include deep sequencing with an automated sequencer to characterize insertion sites, and expression array analysis of T-cell clones to assay for gene expression alterations within 100 kb of the insertion sites.
Evaluate the overall, long-term safety of lentiviral gene transfer. This will include complete clinical evaluation of any AEs resulting from the gene transfer procedure. If any oncogenic event is seen, this evaluation will include complete molecular characterization of the tumor clone including insertion site analysis, gene expression analysis, and evaluation for the LMO2, Cdkn2a, Notch1, Cyclin D2 gene alterations.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment	Experimental	Genetic: CL20-i4-EF1α-hγc-OPT, Drug: Busulfan, Device: CliniMacsParticipants will undergo a bone marrow harvest in the operating room to obtain bone marrow cells. Cells will be isolated and purified utilizing the CliniMacs device. These cells will undergo vector transduction with the lentiviral vector that contains a normal copy of the γc gene gene (CL20-i4-EF1α-hγc-OPT) and then the transduced cells will be reinfused back into the patient. Participants will receive a conditioning regimen of busulfan 3 days prior and 2 days prior to infusion of vector-corrected cells.intervention: CL20-i4-EF1α-hγc-OPT

Who may qualify

Ages: Up to 24 months
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (15 listed)

Treatment Eligibility Criteria:
Age <2 years at the time of enrollment.
No prior therapy with allogeneic stem cell transplantation.
A clinical diagnosis of SCID-X1 documented in the medical record.
A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA.

Key exclusion criteria (0 listed)

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
CL20-i4-EF1α-hγc-OPTAlso: self inactivating lentiviral vector, IND 14570Participants will undergo infusion with autologous CD34+ bone marrow cells transduced with a lentiviral vector that contains a normal copy of the human γc gene.	Genetic	Treatment
BusulfanAlso: Busulfex®, Myleran®Given intravenously (IV).	Drug	Treatment
CliniMacsIsolation and purification of CD34+ stem cells will be done after the unmodified frozen backup is obtained and in accordance with our FDA IND and in accordance with the CliniMacs manual of operations.	Device	Treatment

Primary outcome

Number of patients with adequate cell collection and processing
Time frame: Day 0
The number of patients who underwent no more than two bone marrow harvests and cryopreservation of at least 1.0 million cells/kg following vector transduction.
Number of patients with adequate neutrophil count recovery after busulfan conditioning
Time frame: Day 42 post gene transfer
Adequate recovery is defined as absolute neutrophil count (ANC) >500 cells/μl by day +42 unless the patient is neutropenic prior to busulfan administration.
Number of patients without Grade 4 adverse event (AE)
Time frame: 42 days post gene transfer
The number of patients experiencing no directly related grade 4 or greater adverse event.
Number of patients with successful reconstitution
Time frame: 42 days post gene transfer
Reconstitution with transduced cells defined as detection of vector-marked peripheral blood cells by real time PCR at or above 0.02% VCN in total WBC.
Number of patients with treatment failure
Time frame: 42 days post gene transfer
Treatment failure will be defined as lack of adequate cell collection and processing, lack of neutrophil count recovery by day +42, occurrence of grade 4 or greater toxicities by day +42, and/or lack of detection of >0.02% transduced cells in peripheral blood by day +42 post gene transfer.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
Derived from this study: PubMed 30995372Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long-Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, Sorrentino BP. Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med. 2019 Apr 18;380(16):1525-1534. doi: 10.1056/NEJMoa1815408.
St. Jude Children's Research HospitalLink provided by the sponsor.
Clinical Trials Open at St. JudeLink provided by the sponsor.

Related trials for Severe Combined Immunodeficiency Disease, X-linked

RecruitingPhase 1/2
Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
X-linked Severe Combined Immunodeficiency (XSCID)
Not yet recruitingPhase 1/2
SCID-X1 Gene Therapy Via Intravenous Lentiviral (Ivlv-X1) Injection
SCID, X-Linked
RecruitingObservational study
Evaluation of Patients With Immune Function Abnormalities
Chronic Granulomatous Disease (CGD), X-Linked Severe Combined Immune Deficiency (XSCID)
Enrolling by invitationPhase 1/2
Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy
X-linked Severe Combined Immunodeficiency, X-SCID
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome

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. This study is not recruiting at the moment.

Stephen Gottschalk, MD principal investigator

St. Jude Children's Research Hospital

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 15 inclusion and 0 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: paused, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with adequate cell collection and processing (time frame: Day 0). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01512888, which also lists 1 linked publication.

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 10 Nov 2025.