Phase 1/2: CD45RA Depleted Stem Cell Addback to Prevent Viral or Fungal Infections Post TCRab/CD19 Depleted HSCT
Phase 1/2 Study: CD45RA Depleted Peripheral Stem Cell Addback to Prevent Viral and Fungal Infections Following Alternative Donor TCRab/CD19 Depleted Hematopoietic Stem Cell Transplant
Children's Hospital of Philadelphia
100 participants
Mar 21, 2025
INTERVENTIONAL
Conditions
Summary
The major morbidities of allogeneic hematopoietic stem cell transplant (HSCT) using donors that are not human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life- threatening infections. T cell receptor alpha beta (TCRαβ) T lymphocyte depletion and CD19+ B lymphocyte depletion of alternative donor hematopoietic stem cell (HSC) grafts is effective in preventing GVHD, but immune reconstitution may be delayed, increasing the risk of infections. The central hypothesis of this study is that an addback of CD45RO memory T lymphocytes, derived from a fraction of the original donor peripheral stem cell product depleted of CD45RA naïve T lymphocytes, will accelerate immune reconstitution and help decrease the risk of infections in TCRab/CD19 depleted PSCT.
Eligibility
Inclusion Criteria6
- Disease for which allogeneic HSCT may be curative.
- Remission status of hematologic malignancies and additional disease-specific eligibility determinations will be according to standards of practice within the CHOP Cellular Immunotherapy and Transplant Program (CTTS).
- Patients must be 25 years of age and less
- Evaluation for organ and infectious status as per our CTTS standard operating procedure.
- Signed consent by parent/guardian or able to give consent if 18 years of age and older.
- Participants of childbearing potential must have a negative pregnancy test as per institutional SOP.
Exclusion Criteria17
- Patients who have 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.
- Donor selection and eligibility:
- Unrelated donor meets National Marrow Donor Program criteria for donation.
- Related donor (at least haploidentical) willing and able to donate mobilized peripheral stem cells.
- HLA testing/matching
- HLA testing to be done by molecular methods for A, B, C, DRB1, DQB1
- Related donor: Must be ≥ 5/10 match
- Unrelated donor: 10/10 or 9/10 match
- KIR typing for haploidentical donor for hematologic malignancies
- Donor specific HLA antibodies (DSA) should be assessed for all subjects receiving an HLA mismatched graft (≤ 9/10).
- Donor must be willing to undergo granulocyte colony stimulating factor (GCSF) mobilization and peripheral blood stem cell collection
- Donors must be willing to sign consent to participate in this study.
Interventions
Patients in the first dose level for the CD45RA depleted addback will receive 1 X 10\^6 CD45RO+ T cells/kg. Once all patients in this dose group have been evaluated for acute GVHD at day 100, then we will advance to the next dose level if indicated by safety analysis.
Patients in the second dose level for the CD45RA depleted addback will receive 2 X 10\^6 CD45RO+ T cells/kg. Once all patients in this dose group have been evaluated for acute GVHD at day 100, then we will advance to the next dose level if indicated by safety analysis.
Patients in the third and final dose level for the CD45RA depleted addback will receive 5 X 10\^6 CD45RO+ T cells/kg. All patients in this dose group will be evaluated for acute GVHD at day 100. Based on these findings, the maximum tolerated dose (MTD) will be determined. Once MTD for the addback cell dose has been determined in Phase 1, subjects with mismatched related donors will then enroll in Phase 2.
Patients with mismatched related donors will receive the CD45RA depleted addback at the maximum tolerated dose determined in the Phase 1 portion of the study.
Patients with unrelated donors will receive the CD45RA depleted addback at the dose 5 X 10\^6 CD45RO+ T cells.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06839456