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

NCT06839456 | Recruiting Phase 1 DMC FDA Device

• 1 other identifier: 24-022264
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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); Relapsed Non-Hodgkin Lymphoma; Acquired Aplastic Anemia; Inherited BMF Syndrome; Immunodeficiency; Primary Immune Regulatory Disorder; Hemoglobinopathies; Bone Marrow Failure; Inborn Errors of Metabolism; HLH

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Evaluate number of patients with acute graft vs host disease (aGVHD)

  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)

  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 Outcomes (2)

• Evaluate time to immune reconstitution

  2 years

• Evaluate number of patients with viral reactivation

  2 years

Study Arms (3)

Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)

EXPERIMENTAL

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; Device: Phase 1 Dose Level 2; Device: Phase 1 Dose Level 3

Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRD

EXPERIMENTAL

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

Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donors

EXPERIMENTAL

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

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:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)

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:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)

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 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD)

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:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRD

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.

Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donors

Eligibility Criteria

• Age: 1 Month - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Publications (16)

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Related Links

• U.S. Food \& Drug Administration (2021) Drug Development Tools: Fit-for-Purpose Initiative

MeSH Terms

Conditions

Leukemia; Anemia, Refractory, with Excess of Blasts; Lymphoma, Non-Hodgkin; Congenital Bone Marrow Failure Syndromes; Immunologic Deficiency Syndromes; Hemoglobinopathies; Bone Marrow Failure Disorders; Metabolism, Inborn Errors

Interventions

Clinical Trials, Phase I as Topic

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Timothy Olson, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Atkinson

CONTACT

215-590-2820; cttsbmtintake@chop.edu

Linda Zitkus, BSN,RN

CONTACT

zitkusl@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Hematopoietic Stem Cell Transplantation (HSCT) Program

Model Details: Use of CliniMACS based system for TCRαβ/CD19 Depleted Peripheral Stem Cells and CD45RA Depleted Peripheral Stem Cell Addback. Approximately 90% of the peripheral stem cell (PSC) product will be processed using the CliniMACS system for TCRαβ and CD19 cell depletion. In addition, approximately 10% of the PSCs will undergo CD45RA depletion also using the CliniMACS system. Processing is completed in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique.

Study Record Dates

• First Submitted: February 16, 2025
• First Posted: February 21, 2025
• Study Start: March 21, 2025
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2032
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)