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

  • End date
    Jul 1, 2028
  • participants needed
  • sponsor
    St. Jude Children's Research Hospital
Updated on 23 October 2022
graft versus host disease
ejection fraction
cell transplantation
transplant conditioning
glomerular filtration rate
antithymocyte globulin
severe combined immunodeficiency


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.


In this study, the investigators propose to investigate T and B cell recovery using peripheral blood manipulation that removes potentially Graft-Versus-Host-Disease (GVHD) inducing α/β and CD45RA+ T cells, while still providing potentially beneficial donor γδ and memory T cells.

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.

Condition Severe Combined Immunodeficiency
Treatment busulfan, Fludarabine, thiotepa, CliniMACs, Donor Lymphocyte Infusion, Anti-thymocyte globulin (rabbit)
Clinical Study IdentifierNCT03597594
SponsorSt. Jude Children's Research Hospital
Last Modified on23 October 2022


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