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 range2 Months

SexALL

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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 …

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