Active — Not RecruitingPhase 1/2

Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)

United States4 participantsStarted 2021-09-02

Plain-language summary

Infants with severe combined immunodeficiency (SCID) have a profound decrease in number and function of immune cells, and therefore remain highly vulnerable to infection. If not corrected this often leads to death. Hematopoietic cell transplantation (HCT) from matched sibling donor is the standard treatment for these patients, unfortunately though; most SCID patients lack a sibling donor. Building upon experience and existing data, the investigators are proposing a trial the goals of which are: to provide a conditioning regimen that is well tolerated, and provision of immune cells that altogether should establish rapid immune recovery providing protection from life threatening infections without increasing the risk of dangerous Graft-Versus-Host-Disease. Primary Objectives 1. To evaluate the safety of a TCRα/β/CD19-depleted graft with CD45RA-depleted DLI in infants with SCID 2. To estimate overall survival at 1 year post transplantation Exploratory Objectives 1. To evaluate the significant donor T cell reconstitution of a TCRα/β/CD19 depleted graft with CD45RA-depleted DLI at 1 year (+/-2 weeks). 2. To evaluate engraftment at day 30, 100, month 6, and years 1 to 10 post HCT. 3. To evaluate B cell reconstitution at years 1 to 10 post HCT. 4. To evaluate biomarkers of immune reconstitution at day 30, 60 100, month 6 and years 1 to 10; e.g. immunophenotype (including epigenetic profiling) of T, B, and NK cells, and assays to determine their function. 5. To evaluate clinical outcomes, post HCT. 6. To define the incidence and severity of acute (at day 100, month 6), and chronic (month 6, 12, 24) GVHD following HCT.

Who can participate

Age range

2 Months

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria - Transplant Recipient * Age ≥2 months old at the time of chemotherapy administration * A proven mutation as defined by direct sequencing of patient DNA * Has a suitable matched sibling donor or matched unrelated donor (8/8) or single haplotype matched (≥3 of 6) family member donor * Patient must fulfill pre-transplant evaluation: * Left ventricular ejection fraction \>40% and no evidence of uncorrected congenital malformation with clinical symptomatology * Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2 or serum Creatinine ≤1.2mg/dL * Resting pulse oximetry ≥90% on room or ≥95% on oxygen supplementation * Lansky (age-dependent) performance score ≥50 * Bilirubin ≤3 times the upper limit of normal for age * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age Exclusion Criteria - Transplant Recipient * Positive for HIV infection by genome PCR * Presence of active malignancy * A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care * Presence of a medical condition indicating that survival will be dismal 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 Inclusion Criteria - Matched Sibling Donor and Haplocompatible Donor * Fully matched sibling donor (8/8), or matched …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Number of treatment related deaths

Timeframe: 42 days post DLI

Number of overall grade 3-4 acute Graft-Versus-Host-Disease (GVHD)

Timeframe: 42 days post DLI

Overall Survival(OS)

Timeframe: 1 year post transplant

Trial details

NCT IDNCT03597594

SponsorSt. Jude Children's Research Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-07-01

View on ClinicalTrials.gov More Severe Combined Immunodeficiency trials