Haplocompatible Transplant Using TCRα/β Depletion Followed by CD45RA-Depleted Donor Lymphocyte Infusions for Severe Combined Immunodeficiency (SCID)
NCT ID: NCT03597594
Last Updated: 2025-07-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
4 participants
INTERVENTIONAL
2021-09-02
2028-07-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Transplantation of Hematopoietic Cells in Children With Severe Combined Immunodeficiency Syndrome
NCT00152100
Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation
NCT02790515
Matched Related and Unrelated Donor Stem Cell Transplantation for Severe Combined Immune Deficiency (SCID): Busulfan-based Conditioning With h-ATG, Radiation, and Sirolimus
NCT04370795
Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants
NCT01512888
SCID Bu/Flu/ATG Study With T Cell Depletion
NCT02127892
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Donors will undergo a standard hematopoietic progenitor cell (HPC) mobilization regimen consisting of 5 days of G-CSF given subcutaneously at 10 micrograms/kilogram. The graft will be collected by leukapheresis on days 5 and if needed 6 of G-CSF. The HPC product(s) will be T-cell depleted (TCD) using the investigational CliniMACS device.
The initial HPC product(s) will be split into two portions; one portion will be used for TCR TCRαβ/CD19 depletion and the second portion for CD45depleted DLI product.
1. TCRα/β/CD19-depleted stem cell transplant: All participants will undergo a preparative regimen based on the type of Severe Combined Immunodeficiency (SCID) they have. This is followed by infusion of TCRα/β/CD19-depleted donor cells (with the exception of participants who undergo matched sibling donor HCT).
2. Donor Lymphocyte Infusion (CD45depleted DLI product): Participants, other than those who undergo matched sibling HCT transplant, will receive one dose of CD45RA depleted DLI infusion post TCRα/β/CD19-depleted graft infusion.
During the Phase I portion of the study, up to 4 different dose levels of CD45depleted DLI product will be evaluated.
On the Phase II portion of the study, all participants will receive the Phase I determined maximum tolerated dose (MTD) of DLI.
Participants on both the Phase I and Phase II portions of the study that are unable to receive protocol defined dosing of DLI due to insufficient dose generated will be eligible to receive the entirety of the generated product.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
TCRα/β/CD19-depleted SCT
A preparative regimen based on the type of SCID will be given followed by infusion of donor cells. Cells for infusion are prepared using the CliniMACS System
Regimen 1 - IL2RG, JAK 3 (Haplocompatible) and all MSD
ATG (rabbit) IV Days -9 -8 and -7, Rest Days -6 and -5, Busulfan IV Days -4, -3, and -2, Rest Day -1, TCRα/β/CD19-depleted SCT, Day 0
Regimen 2 - RAG1, RAG2 (Haplocompatible)
ATG (rabbit) IV Days -9 -8 and -7, Fludarabine IV Days -7, -6, -5 and -4, Busulfan IV Days -5, -4 and -3, Thiotepa IV twice daily, Day -2, Rest Day -1, TCRα/β/CD19-depleted SCT, Day 0
Regimen 3 - ADA, IL7R, CD45 deficiency, CD3 subunits (Haplocompatible)
ATG (rabbit) IV Days -9 -8 and -7, Fludarabine IV Days -7, -6, -5 and -4, Busulfan: IV Days -4, -3 and -2, Rest Day -1, TCRα/β/CD19-depleted SCT, Day 0
Anti-thymocyte globulin (rabbit)
given intravenously
Busulfan
given intravenously
Fludarabine
given intravenously
Thiotepa
given intravenous infusion
CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Donor Lymphocyte Infusions
Phase I:
On the Phase I portion of the study, up to 4 different dose levels will be evaluated: Dose level -1, Dose ≥0.1 to ≤0.3; Dose level 1, Dose \>0.3 to ≤0.56; Dose level 2, Dose \>0.56 to ≤1.8; Dose level 3, Dose \>1.80 to ≤3.0
Dosing is determined based on the number of CD3+CD45RA-cells/kg and the patient weight in kilograms.
Phase II:
Participants will receive the Phase I determined maximum tolerated dose (MTD) of DLI.
Cells for infusion are prepared using the CliniMACS System.
CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Donor Lymphocyte Infusion
given intravenous infusion
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Anti-thymocyte globulin (rabbit)
given intravenously
Busulfan
given intravenously
Fludarabine
given intravenously
Thiotepa
given intravenous infusion
CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Donor Lymphocyte Infusion
given intravenous infusion
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* Fully matched sibling donor (8/8), or matched unrelated donor (8/8), or at least single haplotype matched (≥3 of 6) family member
* At least 1 year old (MSD) and at least 18 years of age (Haplocompatible)
* HIV negative
* Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female)
* Not breast feeding
* Regarding donation eligibility, is identified as either:
* Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
* Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271
Exclusion Criteria
* 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
2 Months
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
St. Jude Children's Research Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Ewelina Mamcarz, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Countries
Review the countries where the study has at least one active or historical site.
Related Links
Access external resources that provide additional context or updates about the study.
St. Jude Children's Research Hospital
Clinical Trials Open at St. Jude
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
SCIDBMT
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.