Prophylactic TCRaB+ and CD19+ Depleted Donor Lymphocyte Infusion After Allogeneic Stem Cell Transplant in High-Risk Patients With Hematologic Malignancies

NCT07285668 | Recruiting DMC FDA Device

• 4 other identifiers: 2025-1405UW25034Protocol Version 8/8/25SMPH/MEDICINE/HEM-ONC
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to assess the safety and determine the maximum tolerable dose (MTD) of TCRαβ+/CD19+-depleted Donor Lymphocyte Infusion (αβT/B dep-DLI) after allogeneic stem cell transplant (allo-SCT) in highrisk patients with hematologic malignancies.

Conditions

Hematologic Malignancies

Keywords

allogeneic donor; Lymphocyte Infusion

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs) from DLI to day 28 post-DLI

  To assess safety of prophylactic TCRαβ+/CD19+ depleted donor lymphocyte infusion (αβT/B dep-DLI) after allogeneic stem cell transplant (allo-SCT) in high-risk patients with hematologic malignancies, incidence of AEs will be reported.

  up to day 28 post-DLI (approximately day 63 on study)

• Maximum Tolerated Dose or Maximum Administered Dose

  MTD/MAD defined as the highest dose level at which less than 2 of 6 participants experience a DLT.

  up to day 28 post-DLI (approximately day 63 on study)

Secondary Outcomes (12)

• Incidence of grade II-IV acute Graft-versus-Host Disease (aGVHD) after αβT/B dep-DLI

  up to day 28 post-DLI (approximately day 63 on study)

• Cumulative incidence of severe grade III-IV aGVHD after αβT/B dep-DLI

  up to day 28 post-DLI (approximately day 63 on study)

• Chronic Graft-versus-Host Disease (GVHD) incidence after αβT/B dep-DLI

  up to day 28 post-DLI (approximately day 63 on study)

• Efficacy assessed by 1 year Progression Free Survival (PFS)

  up to 1 year

• Efficacy Assessed by Non-Relapse Mortality

  up to 2 years

Other Outcomes (2)

• Number of regulatory T cells

  up to 2 years

• Measurable Residual Disease (MRD)

  up to 2 years

Study Arms (4)

Dose Escalation Cohort Level 1

EXPERIMENTAL

1 x 10\^6 CD3-CD56+/kg

Device: Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells

Dose Escalation Cohort Level 2

EXPERIMENTAL

2 X 10\^6 CD3-CD56+/kg

Device: Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells

Dose Escalation Cohort Level 3

EXPERIMENTAL

5 X 10\^6 CD3-CD56+/kg

Device: Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells

Dose Escalation Cohort Level -1

EXPERIMENTAL

0.5 x 10\^6 CD3-CD56+/kg Dose to be used only if Dose Level 1 is not tolerated.

Device: Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells

Interventions

Allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells DEVICE

Single intravenous dose of allogeneic donor TCRαβ+/CD19+ cell-depleted peripheral blood mononuclear cells (i.e., αβT/B dep-DLI), where the dose is based on the natural killer (NK) cell (CD3-CD56+) content in the DLI product. Each participant will receive one of four DLI doses depending upon cohort to which the participant is enrolled.

Dose Escalation Cohort Level -1; Dose Escalation Cohort Level 1; Dose Escalation Cohort Level 2; Dose Escalation Cohort Level 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with high-risk myeloid or lymphoid malignancies determined to be eligible to undergo a related, allo-SCT using Disease Risk Index (DRI), including the conditions listed below. These criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning:
• Refractory acute myelogenous or lymphoid leukemia
• Relapsed acute myelogenous or lymphoid leukemia
• Myelodysplastic syndromes with 5 percent or more blasts
• Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase
• Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant
• High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen
• Other high risk hematologic malignancies for which allo-SCT is deemed clinically necessary per PI and based on institutional standards
• The donor for the allo-SCT will have been identified prior to participant recruitment and must be:
• Related AND
• Matched OR mismatched OR haploidentical at Human Leukocyte Antigen (HLA) HLA-A, -B, -C, and -DRB1 by molecular methods
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• Ability to understand and willingness to sign written informed consent document
• Willing to comply with all study procedures and be available for the duration of the study
• Individuals in sexual relationships that could result in pregnancy or impregnation of their partner must use an acceptable method of contraception§ from enrollment until 4 weeks after completing study treatment.

You may not qualify if:

• Poor organ function as follows (According to the pre-transplant workups results):
• Creatinine greater than or equal to 2.0 mg/dL
• Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) greater than or equal to 5 x Upper Limit of Normal (ULN). Liver biopsy per clinician discretion.
• Bilirubin greater than or equal to 3 x ULN (unless Gilbert's syndrome)
• Diffusing capacity of the Lungs for Carbon Monoxide (DLCO) less than 50 percent corrected for hemoglobin
• Left ventricular ejection fraction or shortening fraction less than 40 percent
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

UW Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

Related Links

• Stem Cell and Regenerative Medicine Center

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jacques Galipeau, MD, FRCP(C)

  UW School of Medicine and Public Health

  STUDY DIRECTOR

• Hongtao Liu, MD, PhD

  UW Carbone Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, phase I 3x3 dose-escalation study with expansion cohort, open label, non-randomized, non-placebo controlled, single-group assignment study.

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: December 16, 2025
• Study Start: February 26, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2031
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 5 years after the completion of the primary endpoint

Locations

US (1)