SCIDPhase 2CSIDENCT03619551
Conditioning SCID Infants Diagnosed Early
A Phase 2 study testing Busulfan and Cell processing for TCRαβ+/CD19+ depletion in people with SCID, run by Center for International Blood and Marrow Transplant Research at 38 sites in 2 countries.
Trial summary
The investigators want to study if lower doses of chemotherapy will help babies with SCID to achieve good immunity with less short and long-term risks of complications after transplantation. Read more about this study
- Who is it for?
- Ages 0 to 2 years
- Conditions the study is for
- SCID
- What is being tested?
- Busulfan and Cell processing for TCRαβ+/CD19+ depletion
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 38 sitesin 2 countries
- Study dates
- 22 Oct 2018to 1 Dec 2028
- Phase
- Phase 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 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 1. Infants with SCID, either typical or leaky or Omenn syndrome.
- Typical SCID is defined as either of the following
- Absence or very low number of T cells (CD3+ T cells <300/microliter AND no or very low T cell function (<10% of lower limit of normal) as measured by response to phytohemagglutinin OR
- Presence of maternally derived T cells
- Leaky SCID is defined as the following
- Absence of maternally derived T cells
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- AND either one or both of the following (i, ii): i) <50% of lower limit of normal T cell function as measured by response to PHA OR <30% of lower limit of normal T cell function as measured by response to CD3 ii) Absent or <10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (must document post vaccination or exposure for this criterion to apply)
- AND at least two of the following (i through iii): i) CD3 T cells < 1500/microliter ii) >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (at < 4 years of age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower level of normal.
- Omenn syndrome • Generalized skin rash
- Maternal lymphocytes tested for and not detected.
- >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (<2 years of age)
- Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to antigens (Candida, tetanus) to which the patient has been exposed IF: Proliferation to antigen was not performed, but at least 4 of the following 8 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the patient is eligible as Omenn Syndrome.
- Hepatomegaly
- Splenomegaly
- Lymphadenopathy
- Elevated IgE
- Elevated absolute eosinophil count
- *Oligoclonal T cells measured by CDR3 length or flow cytometry (upload report)
- *Proliferation to PHA is reduced to < 50% of lower limit of normal (LLN) or SI < 30
- *Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells below the lower level of normal
- 2. Documented mutation in one of the following SCID-related genes
- Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1, RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a suitable donor and graft source
- Haploidentical related mobilized peripheral blood cells
- 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment
- Note: to ensure appropriate hepatic metabolism, age at time of busulfan start:
- For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks
- 6. Adequate organ function defined as:
- Cardiac:
- Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥ 26% by echocardiogram.
- Hepatic:
- Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and ALT < 5.0 x ULN for age.
- Renal:
- GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is < 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be > 50 mL/min/1.73 m2.
- Pulmonary No need for supplemental oxygen and O2 saturation > 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care).
Who cannot join
- Presence of any serious life-threatening or opportunistic infection at time of enrollment and prior to the initiation of the preparative regimen. Serious infections as defined below that occur after enrollment must be reported immediately to the Study Coordinating Center, and enrollment will be put on hold until the infection resolves. Ideally enrolled subjects will not have had any infection. If patients have experienced infections, these must have resolved by the following definitions:
- Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site must be negative and patient has completed appropriate course of antibacterial therapy (typically at least 10 days).
- Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days).
- Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of antibacterial therapy (typically at least 10 days). If possible, radiographic resolution should also be demonstrated.
- Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat culture(s) from same site is negative and patient has completed appropriate course of antifungal therapy (typically at least 14 days). The patient may be continued on antifungal prophylaxis following completion of the treatment course.
- Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed appropriate course of therapy (typically at least 21 days). If possible, radiographic resolution should also be demonstrated. The patient may be continued on prophylaxis following completion of the treatment course.
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- Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must be re-tested and are negative.
- If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible, radiographic resolution should also be demonstrated.
- Patients with HIV or HTLV I/II infection will be excluded.
Trial locations and contacts
38 sites in 2 countries.
38 sites in 2 countries
United States35 sites
The University of Michigan
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, 30329
University of Colorado - Children's Hospital
Aurora, Colorado, 80045
Univeristy of Alabama at Birmingham
Birmingham, Alabama, 35294
Dana Farber Cancer Institute - Peds
Boston, Massachusetts, 02115
Levine Children's Hospital
Charlotte, North Carolina, 28203
Comer Children's Hospital/University of Chicago Medicine
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Medical Center Dallas
Dallas, Texas, 75235
Duke University Medical Center; Pediatric Blood and Marrow Transplant
Durham, North Carolina, 27705
Shands HealthCare & University of Florida
Gainesville, Florida, 32610
Helen DeVos Children's
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Children's Hospital Los Angeles
Los Angeles, California, 90027
UCLA Center for Health Sciences
Los Angeles, California, 90095
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
University of Miami/Jackson Memorial Hospital
Miami, Florida, 33136
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota Blood and Marrow Transplant Program - Pediatrics
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Children's Hospital / LSUHSC
New Orleans, Louisiana, 70118
Morgan Stanley Children's Hospital of New York-Presbyterian - Columbia University Medical Center
New York, New York, 10032
Nebraska Medicine
Omaha, Nebraska, 68198
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Mayo Clinic Arizona and Phoenix Children's Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239-3098
Cohen Children's Medical Center
Queens, New York, 11040
Utah Blood and Marrow Transplant Program-Peds
Salt Lake City, Utah, 84112
Rady Children's Hospital, San Diego
San Diego, California, 92123
University of California San Francisco Medical Center - Peds
San Francisco, California, 94143
Fred Hutchinson Cancer Center / Seattle Children's
Seattle, Washington, 98109
All Children's Hospital
St. Petersburg, Florida, 33701
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Canada3 sites
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Montreal, QC
The Hospital for Sick Children
Toronto, Ontario, M5G 1E8
Cancer Care Manitoba/University of Manitoba
Winnipeg, Winnipeg, MB
About this study
Official title: A Randomized Trial of Low Versus Moderate Exposure Busulfan for Infants With Severe Combined Immunodeficiency (SCID) Receiving TCRαβ+/CD19+ Depleted Transplantation: A Phase II Study by the Primary Immune Deficiency Treatment Consortium (PIDTC) and Pediatric Blood and Marrow Transplant Consortium (PBMTC)
The investigators want to study if lower doses of chemotherapy will help babies with SCID to achieve good immunity with less short and long-term risks of complications after transplantation. This trial identifies babies with types of immune deficiencies that are most likely to succeed with this approach and offers them transplant early in life before they get severe infections or later if their infections are under control. It includes only patients receiving unrelated or mismatched related donor transplants.
The study will test if patients receiving transplant using either a low dose busulfan or a medium dose busulfan will have immune recovery of both T and B cells, measured by the ability to respond to immunizations after transplant. The exact regimen depends on the subtype of SCID the patient has. Donors used for transplant must be unrelated or half-matched related (haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T cells removed, using a newer, experimental approach of a well-established technology. Once the stem cell transplant is completed, patients will be followed for 3 years. Approximately 9-18 months after the transplant, vaccinations will be administered, and a blood test measuring whether your child's body has responded to the vaccine will be collected.
Read the detailed description
This is a prospective, multicenter, phase II, open-label study of two reduced busulfan dose levels in newborns identified at birth with SCID of appropriate genotype/phenotype and clinical status, undergoing either haploidentical related or well-matched unrelated donor TCRαβ+/CD19+ depleted HCT. Subjects will be enrolled on either of 2 strata according to genotype (defects of cytokine receptor function i.e. IL2RG or JAK3 and defects of receptor recombination i.e. RAG1 or RAG2). Thus up to 32 subjects on each of 2 strata or 64 subjects total would be enrolled over 4 years with 3 years follow-up.
Patients with IL2RG/JAK3 would be randomized to receive busulfan targeted either to cumulative exposure of 25-35 mg*h/L or 55-65 mg*h/L with Thymoglobulin. Patients with RAG1/2 would be randomized to receive busulfan targeted to cumulative exposure of 25-35 mg*h/L or 55-65 mg*h/L, in conjunction with fludarabine, thiotepa and Thymoglobulin. Safety/feasibility of the novel TCR αβ+/CD19+ depleted allogeneic HCT strategy will be monitored on an ongoing basis using stopping rules for lack of neutrophil engraftment and other important short-term toxicities.
Donor selection would be determined clinically at the discretion of the treating clinicians at each site. Pharmacokinetic monitoring of busulfan exposure will be performed per local practices at CLIA-certified laboratories. Patients will receive busulfan and pharmacokinetic measurement to individualize dosing. Time-concentration data of the initial dose and subsequent doses will be reviewed centrally (Dr. Janel Long-Boyle) using a cloud-based application (InsightRx) to guide dose adjustment in real-time (Long-Boyle, Chan, Keizer, 2017, ASBMT Tandem abstract accepted). Clinical and laboratory data will be collected at defined time points over 3 years and entered in an electronic data capture system using study-specific case report forms. These data will be used to measure the outcomes including the primary outcome (cAUC of busulfan that promotes humoral immune reconstitution at 2 years post HCT with acceptable regimen-related toxicity at 42 days post HCT) and secondary outcomes (the quality of donor cell engraftment and immune function achieved in B and T cell compartments and survival). Mechanistic studies supporting the exploratory endpoints will be conducted centrally in designated laboratories.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Randomization between low and medium doses of busulfan for TCR αβ+/CD19+ depleted haploidentical related and unrelated donor HCT.
Cell processing for TCRαβ+/CD19+ depletionDevice
Also called CliniMACS
T-cells and B-cells will be removed from the stem cells collected from the donor by an investigational process called alpha-beta CD3+/CD19+ t-cell depletion using a device called CliniMACS® prior to recipient infusion, hopefully minimizing the risk of significant graft vs. host disease (GVHD) or lymphoproliferative disorder.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Busulfan | Experimental | Busulfan based preparative regimen targeted at area-under-the-curve (cAUC) exposure of 25-35 mg*h/L .
Randomization between the two dose levels will be done separately in each genotype stratum (RAG1/RAG2 and IL2RG/JAK3), using permuted blocks. Receives: Drug: Busulfan; Device: Cell processing for TCRαβ+/CD19+ depletion |
| Medium Dose Busulfan | Experimental | Busulfan based preparative regimen targeted at area-under-the-curve (cAUC) exposure of 55-65 mg*h/L.
Randomization between the two dose levels will be done separately in each genotype stratum (RAG1/RAG2 and IL2RG/JAK3), using permuted blocks. Receives: Drug: Busulfan; Device: Cell processing for TCRαβ+/CD19+ depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vaccine specific antibody response
Humoral immune reconstitution by 2 years post HCT, defined by specific antibody response to tetanus toxoid. Criteria for evaluation of humoral immune response are the following:
- Donor T cell chimerism ≥50%
- B cell count ≥50 cells/microliter
- IVIG independent for ≥12 weeks
Subjects meeting the criteria receive 3 doses of tetanus toxoid at least 4 weeks apart, followed by measurement of tetanus titer at least 4-6 weeks after the 3rd dose. Those who achieve tetanus titer of ≥0.15 IU/ml after vaccination will meet the primary endpoint. Patients who have documented humoral immune response at a time prior to 2 years will be considered a success for the primary endpoint, while patients who do not have humoral immune response evaluated by 2 years will be considered failures for the primary endpoint.
Measured: 2 years
Secondary outcomes (8)
Immune Reconstitution
- T cell immune reconstitution at 30 days, 60 days, 3 months, 6 months, 12 months, and 2 years post-HCT.
- Naïve T cell generation and thymic output at 3 months, 6 months, 12 months and 2 years post-HCT.
- Freedom from immunoglobulin substitution will be assessed on all patients at 9 months, 12 months, 2 years and 3 years post-HCT. Patients who have not received IVIG for at least 12 weeks at the time of assessment will be considered free from immunoglobulin substitution.
- Tetanus responses on all patients who complete a trial of vaccination by additional timepoints of 12 months, 18 months and 3 years post-HCT.
- Live vaccine responses on all patients who undergo trial of vaccination by 3 years post-HCT
Measured: Up to 3 years
Engraftment
- Neutrophil engraftment will be assessed on all patients and defined as achieving an absolute neutrophil count of >500 cells/microliter for 3 consecutive days by day 42 post-HCT
- Donor cell chimerism (whole blood, sorted CD3 (T-cell), CD19 (B-cell) and CD56 (NK cell) and granulocyte (CD15)) at 42 days, 3 months, 6 months, 12 months, and 2 years post-HCT. Absolute B cell, NK cell and granulocyte counts will be measured.
Measured: Neutrophil Engraftment: 42 days post-HCT. Donor cell chimerism up to 2 years post-HCT.
Overall Survival
Data to track overall survival will be collected at 1, 2 and 3 years post-HCT.
Measured: 3 years
Event Free Survival
Data to track event free survival will be collected at 1, 2 and 3 years post-HCT. Events will be defined as 1) death from any cause, 2) rejection of the graft (T-cell and/or whole blood chimerism <5% donor), 3) graft failure necessitating a second HCT procedure from the same donor or a different donor, with or without conditioning, 4) DLI given for treatment of falling chimerism.
Measured: 3 years
Acute graft-versus-host disease (aGVHD)
Occurrence of acute (grade II-IV and grade III-IV) GVHD.
Measured: day 100 and 6 months post HCT
Chronic graft-versus-host disease (cGVHD)
Occurrence of chronic GVHD by 6 months, 12 months and 24 months post-HCT.
Measured: 2 years post HCT
Post-HCT Complications
- Infections
- Targeted regimen related toxicity (severe veno-occlusive disease of the liver, idiopathic pneumonitis syndrome)
- Autoimmunity
Measured: Up to 2 years post-HCT
Busulfan Pharmacokinetics
Blood samples will be collected on busulfan dosing days 1 and 3 at 2.35, 4, 6 and 8 hours from the time of the start of the infusion. The results will be used to estimate individual exposure (AUC and cAUC).
Measured: Pre-HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start22 Oct 2018
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SCIDStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomization will be performed after eligibility is confirmed. Randomization between the two busulfan dose levels will be done separately in each genotype stratum, using permuted blocks. Randomization will be stratified further by donor type (Haploidentical related vs. Matched Unrelated Donor).
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Center for International Blood and Marrow Transplant Research
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Sung-Yun Pai, MD, Study chair, National Institutes of Health (NIH)Michael Pulsipher, MD, Study chair, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03619551
- Sponsor's protocol ID
- PBMTC NMD1801
- Acronym
- CSIDE
- Status last verified
- Jan 2026
- First submitted
- 16 Jul 2018
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Low Versus Moderate Exposure Busulfan for Infants With Severe Combined Immunodeficiency (SCID) Receiving TCRαβ+/CD19+ Depleted Transplantation: A Phase II Study by the Primary Immune Deficiency Treatment Consortium (PIDTC) and Pediatric Blood and Marrow Transplant Consortium (PBMTC)
- ClinicalTrials.gov ID
- NCT03619551
- Acronym / sponsor ID
- CSIDE / PBMTC NMD1801
- Conditions
- SCID
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Center for International Blood and Marrow Transplant ResearchResearch network
- Study start
- 22 Oct 2018 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 8 Aug 2018 (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.
The investigators want to study if lower doses of chemotherapy will help babies with SCID to achieve good immunity with less short and long-term risks of complications after transplantation. This trial identifies babies with types of immune deficiencies that are most likely to succeed with this approach and offers them transplant early in life before they get severe infections or later if their infections are under control. It includes only patients receiving unrelated or mismatched related donor transplants.
The study will test if patients receiving transplant using either a low dose busulfan or a medium dose busulfan will have immune recovery of both T and B cells, measured by the ability to respond to immunizations after transplant. The exact regimen depends on the subtype of SCID the patient has. Donors used for transplant must be unrelated or half-matched related (haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T cells removed, using a newer, experimental approach of a well-established technology. Once the stem cell transplant is completed, patients will be followed for 3 years. Approximately 9-18 months after the transplant, vaccinations will be administered, and a blood test measuring whether your child's body has responded to the vaccine will be collected.
Detailed description
This is a prospective, multicenter, phase II, open-label study of two reduced busulfan dose levels in newborns identified at birth with SCID of appropriate genotype/phenotype and clinical status, undergoing either haploidentical related or well-matched unrelated donor TCRαβ+/CD19+ depleted HCT. Subjects will be enrolled on either of 2 strata according to genotype (defects of cytokine receptor function i.e. IL2RG or JAK3 and defects of receptor recombination i.e. RAG1 or RAG2). Thus up to 32 subjects on each of 2 strata or 64 subjects total would be enrolled over 4 years with 3 years follow-up.
Patients with IL2RG/JAK3 would be randomized to receive busulfan targeted either to cumulative exposure of 25-35 mg*h/L or 55-65 mg*h/L with Thymoglobulin. Patients with RAG1/2 would be randomized to receive busulfan targeted to cumulative exposure of 25-35 mg*h/L or 55-65 mg*h/L, in conjunction with fludarabine, thiotepa and Thymoglobulin. Safety/feasibility of the novel TCR αβ+/CD19+ depleted allogeneic HCT strategy will be monitored on an ongoing basis using stopping rules for lack of neutrophil engraftment and other important short-term toxicities.
Donor selection would be determined clinically at the discretion of the treating clinicians at each site. Pharmacokinetic monitoring of busulfan exposure will be performed per local practices at CLIA-certified laboratories. Patients will receive busulfan and pharmacokinetic measurement to individualize dosing. Time-concentration data of the initial dose and subsequent doses will be reviewed centrally (Dr. Janel Long-Boyle) using a cloud-based application (InsightRx) to guide dose adjustment in real-time (Long-Boyle, Chan, Keizer, 2017, ASBMT Tandem abstract accepted). Clinical and laboratory data will be collected at defined time points over 3 years and entered in an electronic data capture system using study-specific case report forms. These data will be used to measure the outcomes including the primary outcome (cAUC of busulfan that promotes humoral immune reconstitution at 2 years post HCT with acceptable regimen-related toxicity at 42 days post HCT) and secondary outcomes (the quality of donor cell engraftment and immune function achieved in B and T cell compartments and survival). Mechanistic studies supporting the exploratory endpoints will be conducted centrally in designated laboratories.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomization will be performed after eligibility is confirmed. Randomization between the two busulfan dose levels will be done separately in each genotype stratum, using permuted blocks. Randomization will be stratified further by donor type (Haploidentical related vs. Matched Unrelated Donor).
| Arm | Type | Receives |
|---|---|---|
| Low Dose Busulfan | Experimental | Drug: Busulfan, Device: Cell processing for TCRαβ+/CD19+ depletionBusulfan based preparative regimen targeted at area-under-the-curve (cAUC) exposure of 25-35 mg*h/L . Randomization between the two dose levels will be done separately in each genotype stratum (RAG1/RAG2 and IL2RG/JAK3), using permuted blocks. |
| Medium Dose Busulfan | Experimental | Drug: Busulfan, Device: Cell processing for TCRαβ+/CD19+ depletionBusulfan based preparative regimen targeted at area-under-the-curve (cAUC) exposure of 55-65 mg*h/L. Randomization between the two dose levels will be done separately in each genotype stratum (RAG1/RAG2 and IL2RG/JAK3), using permuted blocks. |
Who may qualify
- Ages
- 0 to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (34 listed)
- 1. Infants with SCID, either typical or leaky or Omenn syndrome.
- Typical SCID is defined as either of the following
- Leaky SCID is defined as the following
- Omenn syndrome • Generalized skin rash
- 2. Documented mutation in one of the following SCID-related genes
Key exclusion criteria (9 listed)
- Presence of any serious life-threatening or opportunistic infection at time of enrollment and prior to the initiation of the preparative regimen. Serious infections as defined below that occur after enrollment must be reported immediately to the Study Coordinating Center, and enrollment will be put on hold until the infection resolves. Ideally enrolled subjects will not have had any infection. If patients have experienced infections, these must have resolved by the following definitions:
- Patients with HIV or HTLV I/II infection will be excluded.
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 |
|---|---|---|
| BusulfanRandomization between low and medium doses of busulfan for TCR αβ+/CD19+ depleted haploidentical related and unrelated donor HCT. | Drug | Low Dose Busulfan, Medium Dose Busulfan |
| Cell processing for TCRαβ+/CD19+ depletionAlso: CliniMACST-cells and B-cells will be removed from the stem cells collected from the donor by an investigational process called alpha-beta CD3+/CD19+ t-cell depletion using a device called CliniMACS® prior to recipient infusion, hopefully minimizing the risk of significant graft vs. host disease (GVHD) or lymphoproliferative disorder. | Device | Low Dose Busulfan, Medium Dose Busulfan |
Primary outcome
Vaccine specific antibody response
Time frame: 2 years
Humoral immune reconstitution by 2 years post HCT, defined by specific antibody response to tetanus toxoid. Criteria for evaluation of humoral immune response are the following: * Donor T cell chimerism ≥50% * B cell count ≥50 cells/microliter * IVIG independent for ≥12 weeks Subjects meeting the criteria receive 3 doses of tetanus toxoid at least 4 weeks apart, followed by measurement of tetanus titer at least 4-6 weeks after the 3rd dose. Those who achieve tetanus titer of ≥0.15 IU/ml after vaccination will meet the primary endpoint. Patients who have documented humoral immune response at a time prior to 2 years will be considered a success for the primary endpoint, while patients who do not have humoral immune response evaluated by 2 years will be considered failures for the primary endpoint.
8 secondary outcomes
Immune Reconstitution
Time frame: Up to 3 years
Engraftment
Time frame: Neutrophil Engraftment: 42 days post-HCT. Donor cell chimerism up to 2 years post-HCT.
Overall Survival
Time frame: 3 years
Event Free Survival
Time frame: 3 years
Acute graft-versus-host disease (aGVHD)
Time frame: day 100 and 6 months post HCT
Chronic graft-versus-host disease (cGVHD)
Time frame: 2 years post HCT
Post-HCT Complications
Time frame: Up to 2 years post-HCT
Busulfan Pharmacokinetics
Time frame: Pre-HCT
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 26 Oct 2026.
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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. This study is not recruiting at the moment.
Sung-Yun Pai, MD study chair
National Institutes of Health (NIH)
Michael Pulsipher, MD study chair
University of Utah
38 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Busulfan and Cell processing for TCRαβ+/CD19+ depletion in people with SCID, run by Center for International Blood and Marrow Transplant Research at 38 sites in 2 countries.
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 34 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Canada. 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 phase mean?
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?
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?
Vaccine specific antibody response (time frame: 2 years). 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 26 Oct 2026.