Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children.
I V Zvyagin, I Z Mamedov, O V Tatarinova...
https://pubmed.ncbi.nlm.nih.gov/27811849Actively Recruiting
Phase 1
Phase 2
Age: 1Month - 25Years
All Genders
ID06839456
Phase 1/2 Study of CD45RA Depleted Stem Cell Addback to Prevent Viral and Fungal Infections After Alternative Donor TCRab/CD19 Depleted Hematopoietic Stem Cell Transplant
Led by Children's Hospital of Philadelphia · Updated on 2026-04-15
100
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new approach to prevent serious viral and fungal infections after allogeneic hematopoietic stem cell transplant (HSCT) from donors who are not fully HLA-matched siblings. This study focuses on adding back CD45RO memory T cells to grafts depleted of T cell receptor alpha beta (TCRb1b2) and CD19+ B cells to reduce the risk of graft versus host disease (GVHD) while improving immune recovery. The trial expands eligibility to patients with both malignant and non-malignant conditions using mismatched related and unrelated donors. The study includes phase 1 and phase 2 periods. Phase 1 is a dose escalation study for patients receiving cells from mismatched or haploidentical related donors, testing increasing doses of CD45RA-depleted addback cells to find the maximum tolerated dose. Phase 2 treats patients with this dose from phase 1 or those with unrelated donors using a previously established dose. Stem cell sources are mobilized peripheral blood stem cells, and conditioning follows disease-specific standard care. Participants will be monitored for acute and chronic GVHD up to 2 years after transplant. Their immune recovery and incidence of viral reactivation will also be evaluated over 2 years. Assessments include standard disease and organ criteria, infection status, and consent procedures. The trial duration and safety are closely observed with regular follow-ups to measure outcomes related to immune function and transplant complications.
CONDITIONS
Brief Title
Phase 1/2: CD45RA Depleted Stem Cell Addback to Prevent Viral or Fungal Infections Post TCRab/CD19 Depleted HSCT
Who Can Participate
Age: 1Month - 25Years
All Genders
Eligibility Criteria
You may qualify if you...
- Disease for which allogeneic hematopoietic stem cell transplant (HSCT) may be curative
- Remission status and additional disease-specific eligibility as per standard practice within the CHOP Cellular Immunotherapy and Transplant Program
- Participants must be 25 years of age or younger
- Organ and infection status evaluated according to program standard operating procedures
- Signed consent by parent/guardian or participant if 18 years or older
- Negative pregnancy test for participants of childbearing potential as per institutional procedures
You will not qualify if you...
- Performance score less than 60
- No suitable donor available for mobilized peripheral stem cells
- Patients with Hodgkin lymphoma or non-Burkitt, non-lymphoblastic lymphoma
- Planned receipt of alemtuzumab during conditioning
- Patients with an available 10/10 HLA matched sibling donor
- Patients who do not meet institutional disease, organ, or infectious criteria
- Donors must meet National Marrow Donor Program criteria if unrelated
- Related donors must be at least haploidentical and willing to donate
- Donors must be willing to undergo mobilization and stem cell collection and sign consent
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Implementation
Duration - Up to 100 days post-transplantation
Participants receive a CD45RA depleted stem cell addback after TCRab/CD19 depleted hematopoietic stem cell transplant to help prevent viral and fungal infections. Dose levels vary in Phase 1 to determine the maximum tolerated dose, followed by treatment at the determined dose in Phase 2.
Multiple visits for monitoring during the first 100 days post-transplant
Follow-up
Duration - Up to 2 years post-transplantation
Participants are monitored for acute and chronic graft versus host disease and immune reconstitution for up to 2 years after transplantation.
Periodic visits for up to 2 years
Trial Site Locations
Total: 1 location
1
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
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Research Team
M
Megan Atkinson
L
Linda Zitkus, BSN,RN
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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Published Research Related To This Trial
Memory CD4+ T cells do not induce graft-versus-host disease.
Britt E Anderson, Jennifer McNiff, Jun Yan...
https://pubmed.ncbi.nlm.nih.gov/12840064Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease.
Hong Zheng, Catherine Matte-Martone, Hongmei Li...
https://pubmed.ncbi.nlm.nih.gov/18045967Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis.
D Teschner, E Distler, D Wehler...
https://pubmed.ncbi.nlm.nih.gov/23933765Engineering human peripheral blood stem cell grafts that are depleted of naïve T cells and retain functional pathogen-specific memory T cells.
Marie Bleakley, Shelly Heimfeld, Lori A Jones...
https://pubmed.ncbi.nlm.nih.gov/24525279Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts.
Marie Bleakley, Shelly Heimfeld, Keith R Loeb...
https://pubmed.ncbi.nlm.nih.gov/26053664CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study.
Fabien Touzot, Bénédicte Neven, Liliane Dal-Cortivo...
https://pubmed.ncbi.nlm.nih.gov/25282016Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies.
B M Triplett, D R Shook, P Eldridge...
https://pubmed.ncbi.nlm.nih.gov/25665048Haploidentical stem cell transplantation augmented by CD45RA negative lymphocytes provides rapid engraftment and excellent tolerability.
David R Shook, Brandon M Triplett, Paul W Eldridge...
https://pubmed.ncbi.nlm.nih.gov/25559618Novel treatment of severe combined immunodeficiency utilizing ex-vivo T-cell depleted haploidentical hematopoietic stem cell transplantation and CD45RA+ depleted donor lymphocyte infusions.
Nicholas Brodszki, Dominik Turkiewicz, Jacek Toporski...
https://pubmed.ncbi.nlm.nih.gov/26768987