Prophylactic and Therapeutic DLI-X for Leukemia Relapse After HCT

Summary

The primary objective of this proposal is to conduct the first-in-human randomized clinical trial evaluating prophylactic DLI-X (pro-DLI-X) for relapse prevention following matched sibling donor (MSD) or haploidentical (haplo) hematopoietic cell transplantation (HCT) in patients with hematologic malignancies. Additionally, the study aims to assess the safety and efficacy of therapeutic DLI-X (t-DLI-X) compared to t-DLI alone in patients with minimal residual disease (MRD+) or overt relapse post-alloHCT. For patients with CD19-positive lymphoid malignancies, the study will incorporate blinatumomab, while those with myeloid or CD19-negative lymphoid malignancies will receive t-DLI-X or t-DLI alone.

We hypothesize that both pro-DLI-X and t-DLI-X, with or without blinatumomab, will demonstrate safety and superior efficacy by enhancing graft-versus-leukemia (GvL) effects mediated by natural killer (NK) cells, γδ T cells, and CD8+ T cells, while maintaining manageable and treatment-responsive graft-versus-host disease (GvHD).

Conditions

• Acute Lymphoid Leukemia
• Acute Myeloid Leukemia
• Acute Undifferentiated Leukemia (AUL)
• Myelodysplastic Syndrome
• Chronic Myeloid Leukemia
• Non-Hodgkin Lymphoma

Interventions

BIOLOGICAL

Exercise Mobilized Prophylactic DLI

Pro-DLI-X will be given through the patient's central line at an initial dose of 100,000 CD3+ cells/kilogram (kg) of recipient weight for haploidentical hematopoietic cell transplantation (haploHCT) and 300,000 CD3+ cells/kg for matched sibling donor hematopoietic cell transplantation (MSD HCT). Participants will receive up to 3 doses of pro-DLI-X, and each dose will be increased as follows: dose 2 will be 300,000 CD3+ cells/kg for haploHCT and 1,000,000 CD3+ cells/kg for MSD HCT; dose 3 will be 1,000,000 CD3+ cells/kg for haploHCT and 3,000,000 CD3+ cells/kg for MSD HCT.

BIOLOGICAL

Standard Prophylactic DLI

Pro-DLI will be given through the patient's central line at an initial dose of 100,000 CD3+ cells/kilogram (kg) of recipient weight for haploidentical hematopoietic cell transplantation (haploHCT) and 300,000 CD3+ cells/kg for matched sibling donor hematopoietic cell transplantation (MSD HCT). Participants will receive up to 3 doses of pro-DLI-X, and each dose will be increased as follows: dose 2 will be 300,000 CD3+ cells/kg for haploHCT and 1,000,000 CD3+ cells/kg for MSD HCT; dose 3 will be 1,000,000 CD3+ cells/kg for haploHCT and 3,000,000 CD3+ cells/kg for MSD HCT.

BIOLOGICAL

Exercise Mobilized Therapeutic DLI

t-DLI-X will be given through the patient's central line at an initial dose of 1,000,000 CD3+ cells/kilogram (kg) of recipient weight for haploidentical hematopoietic cell transplantation (haploHCT) and 3,000,000 CD3+ cells/kg for matched sibling donor hematopoietic cell transplantation (MSD HCT). Participants will receive up to 3 doses of t-DLI-X, and each dose will be increased as follows: dose 2 will be 3,000,000 CD3+ cells/kg for haploHCT and 10,000,000 CD3+ cells/kg for MSD HCT; dose 3 will be 10,000,000 CD3+ cells/kg for haploHCT and 30,000,000 CD3+ cells/kg for MSD HCT.

BIOLOGICAL

Standard Therapeutic DLI

t-DLI will be given through the patient's central line at an initial dose of 1,000,000 CD3+ cells/kilogram (kg) of recipient weight for haploidentical hematopoietic cell transplantation (haploHCT) and 3,000,000 CD3+ cells/kg for matched sibling donor hematopoietic cell transplantation (MSD HCT). Participants will receive up to 3 doses of t-DLI-X, and each dose will be increased as follows: dose 2 will be 3,000,000 CD3+ cells/kg for haploHCT and 10,000,000 CD3+ cells/kg for MSD HCT; dose 3 will be 10,000,000 CD3+ cells/kg for haploHCT and 30,000,000 CD3+ cells/kg for MSD HCT.

Sponsors & Collaborators

• University of Arizona

  lead OTHER

Principal Investigators

• Emmanuel Katsanis, MD · University of Arizona

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-31

Primary Completion

2030-06-01

Completion

2030-06-01

FDA Drug

Yes

Countries

• United States

Study Locations