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

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.

Conditions

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

Interventions

DEVICE

Phase 1 Dose Level 3

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.

DEVICE

Phase 2 Maximum Tolerated Dose determined in Phase 1

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.

DEVICE

Phase 2 Established Dose from prior study, NCT03810196

Patients with unrelated donors will receive the CD45RA depleted addback at the dose 5 X 10\^6 CD45RO+ T cells.

DEVICE

Phase 1 Dose Level 1

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.

DEVICE

Phase 1 Dose Level 2

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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia

  lead OTHER

Principal Investigators

• Timothy Olson, MD, PhD · Children's Hospital of Philadelphia

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

1 Month

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-03-21

Primary Completion

2031-03-31

Completion

2032-03-31

FDA Device

Yes

Countries

• United States

Study Locations