Recruiting
Phase 1
Phase 2

CD45RA Depleted

Sponsor:

Children's Hospital of Philadelphia

Code:

NCT06839456

Conditions

Leukemia

High Risk Acute Lymphoblastic Leukemia

High Risk Acute Myeloid Leukemia

Relapse Leukemia

MDS (Myelodysplastic Syndrome)

Eligibility Criteria

Sex: All

Age: 0 - 25

Healthy Volunteers: Not accepted

Interventions

Phase 1 Dose Level 1

Phase 1 Dose Level 2

Phase 1 Dose Level 3

Phase 2 Maximum Tolerated Dose determined in Phase 1

Phase 2 Established Dose from prior study, NCT03810196

Study Details

Brief 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)

Study ID

NCT06839456

Start date

Mar 21, 2025

Status verified date

Apr, 2026

Completion date

Mar, 2032

Anticipated

Primary completion date

Mar, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 25

Healthy Volunteers: Not accepted

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 Design

Enrollment

100 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

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

Interventions

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.

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.

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.

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.

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.

Primary outcome measure

  • Evaluate number of patients with acute graft vs host disease (aGVHD) [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

Megan Atkinson

215-590-2820cttsbmtintake@chop.edu

Linda Zitkus, BSN,RN

zitkusl@chop.edu

Locations

Children's Hospital of Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Megan Atkinson

215-590-2820atkinsonm@chop.edu

More Information

Sponsor

Children's Hospital of Philadelphia

Last update posted

Apr 15, 2026

Last verified

Apr, 2026

Keywords

  • alpha beta T cell depletion
  • CD45RA
  • CD45RO
  • GVHD prevention
  • Memory T cells

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Children's Hospital of Philadelphia on 2026-04-15.