Phase 1/2: CD45RA Depleted Stem Cell Addback to Prevent Viral or Fungal Infections Post TCRab/CD19 Depleted HSCT

Part of paid clinical trials in Philadelphia, Pennsylvania.

Sponsor
Children's Hospital of Philadelphia
Study ID
NCT06839456
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

  • Acquired Aplastic Anemia
  • Bone Marrow Failure
  • HLH
  • Hemoglobinopathies
  • High Risk Acute Lymphoblastic Leukemia
  • High Risk Acute Myeloid Leukemia
  • Immunodeficiency
  • Inborn Errors of Metabolism
  • Inherited BMF Syndrome
  • Leukemia
  • MDS (Myelodysplastic Syndrome)
  • Primary Immune Regulatory Disorder
  • Relapse Leukemia
  • Relapsed Non-Hodgkin Lymphoma

Eligibility Criteria

Sex
ALL
Age
1 Month - 25 Years
Healthy Volunteers
Not accepted

Interventions

  • Phase 1 Dose Level 1 — DEVICE
    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.
  • Phase 1 Dose Level 2 — DEVICE
    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.
  • Phase 1 Dose Level 3 — DEVICE
    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.
  • Phase 2 Maximum Tolerated Dose determined in Phase 1 — DEVICE
    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.
  • Phase 2 Established Dose from prior study, NCT03810196 — DEVICE
    Patients with unrelated donors will receive the CD45RA depleted addback at the dose 5 X 10\^6 CD45RO+ T cells.

Study Details

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.

Key Dates

Start date
Mar 21, 2025
Status verified
Apr 2026
Primary completion
Mar 31, 2031
Completion
Mar 31, 2032

Study Design

Enrollment
100 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)
    Stem cell source: mobilized peripheral blood stem cells (PBSC) Donor type: \> or = 5/10 mismatched related donor Conditioning: disease specific standard of care (SOC) regimens
  • Experimental: Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRD
    Stem cell source: mobilized PBSC Donor type: \> or = 5/10 mismatched related donor Conditioning: disease specific SOC regimens
  • Experimental: Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donors
    Stem cell source: mobilized PBSC Donor type: 9/10 or 10/10 matched unrelated donor Conditioning: disease specific SOC regimens

Primary Outcome Measure

Evaluate number of patients with acute graft vs host disease (aGVHD) [ Time Frame: Up to 100 days post-transplantation ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Children's Hospital of PhiladelphiaPhiladelphiaPennsylvania19104
Megan Atkinson
[email protected]
215-590-2820

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