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

April 13, 2026 updated by: Timothy Olson, Children's Hospital of Philadelphia

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but immune reconstitution is delayed. Important memory T cells that may protect patients from fungal and viral infections are also removed in the T depletion process. CD45RA depletion has been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This single institutional trial builds on data from our protocol #18-015286, NCT03810196, "CD45RA Depleted Peripheral Stem Cell Addback for Patients at Risk for Viral or Fungal Infections Post-TCRαβ/CD19 Depleted Hematopoietic Stem Cell Transplant". This prior protocol was limited to patients with hematologic malignancies using only unrelated donors as the stem cell source.

This new study will broaden the eligible diagnoses to include non-malignant transplant indications and participants with greater than or equal to 5/10 HLA matched related donors (also known as haploidentical).

This will be a phase 1 and phase 2 study depending on the donor type. Phase 1 will include patients receiving cells from mismatched/haploidentical related donors. This will be a dose escalation study to determine the maximum tolerated cell dose of the CD45RA depleted addback. Once that dose is determined, patients with this donor type will be treated as part of phase 2.

Patients receiving their cells from unrelated donors ( 9/10 or 10/10 HLA matched) will be treated as part of phase 2 with the CD45RA depleted addback cell dose that was used on our prior study. Phase 1 and phase 2 will run concurrently.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Disease for which allogeneic HSCT may be curative.
  2. 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).
  3. Patients must be 25 years of age and less
  4. Evaluation for organ and infectious status as per our CTTS standard operating procedure.
  5. Signed consent by parent/guardian or able to give consent if 18 years of age and older.
  6. Participants of childbearing potential must have a negative pregnancy test as per institutional SOP.

Exclusion Criteria:

  1. Patients who have performance score less than 60.
  2. No suitable donor available for mobilized peripheral stem cells.
  3. Patients with Hodgkin lymphoma or non-Burkitt, non-lymphoblastic lymphoma.
  4. Planned receipt of alemtuzumab during conditioning.
  5. Patients with an available 10/10 HLA matched sibling donor.
  6. Patients who do not meet institutional disease, organ or infectious criteria.

Donor selection and eligibility:

  1. Unrelated donor meets National Marrow Donor Program criteria for donation.
  2. Related donor (at least haploidentical) willing and able to donate mobilized peripheral stem cells.

  3. 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).
  4. Donor must be willing to undergo granulocyte colony stimulating factor (GCSF) mobilization and peripheral blood stem cell collection
  5. Donors must be willing to sign consent to participate in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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.
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.
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
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.
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate number of patients with acute graft vs host disease (aGVHD)
Time Frame: Up to 100 days post-transplantation
Safety evaluation assessment by cumulative incidence of acute graft vs host disease (reaction of donor immune cells against host tissues) to determine percentage of patients that develop grade 3-4 aGVHD.
Up to 100 days post-transplantation
Evaluate number of patients with chronic graft vs host disease (cGVHD)
Time Frame: Up to 2 years post-transplantation
Safety evaluation assessment by cumulative incidence and severity of chronic GVHD (graft vs host disease that occurs more than 100 days after transplant) to determine percentage of patients that develop cGVHD.
Up to 2 years post-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate time to immune reconstitution
Time Frame: 2 years
Evaluate time to achievement of standard immune reconstitution benchmarks following TCRαβ/CD19 depleted HSCT with CD45RA+ depleted addback, compared to historical experience with TCRαβ/CD19 depletion alone.
2 years
Evaluate number of patients with viral reactivation
Time Frame: 2 years
Evaluate number of patients with viral reactivation (CMV, adenovirus, EBV, BK) following TCRαβ/CD19 depleted HSCT with CD45RA depleted addback, compared to historical experience with TCRαβ/CD19 depletion alone.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Philadelphia

Investigators

  • Principal Investigator: Timothy Olson, MD, PhD, Children's Hospital of Philadelphia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2025

Primary Completion (Estimated)

March 1, 2031

Study Completion (Estimated)

March 1, 2032

Study Registration Dates

First Submitted

February 16, 2025

First Submitted That Met QC Criteria

February 17, 2025

First Posted (Actual)

February 21, 2025

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-022264

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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