Prophylactic and Therapeutic DLI-X for Leukemia Relapse After HCT

April 1, 2026 updated by: University of Arizona

A Feasibility/Pilot First-in-human Study of Exercise-mobilized NK-enriched Donor Lymphocyte Infusions (DLI-X) to Prevent or Treat Leukemia Relapse After Allogeneic Hematopoietic Cell Transplantation

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

94

Phase

  • 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
    • Arizona
      • Tucson, Arizona, United States, 85719
        • The University of Arizona Cancer Center
        • Contact:
        • Principal Investigator:
          • Emmanuel Katsanis, MD
        • Contact:
        • Sub-Investigator:
          • Richard Simpson, PhD

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
  • Older Adult

Accepts Healthy Volunteers

No

Description

DLI Recipient Inclusion Criteria:

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Male or female, aged 0-65 years
  • Diagnosis of acute leukemia (lymphoid, myeloid or undifferentiated) myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML) or non-Hodgkin's lymphoma (NHL)
  • Undergoing myeloablative or reduced intensity matched sibling donor (MSD) HCT or haploidentical HCT
  • Have a locally available healthy matched or haploidentical (≥5/10 HLA antigen matched) related donor between 12 and 50 years of age, consented and able to perform the exercise sessions. (see donor inclusion criteria)
  • The familial donors will first complete the fitness evaluation to determine VO2max and peak cycling power and following successful completion of the donor evaluation, the patients willing to participate in the randomized trial will be enrolled.

DLI Donor Inclusion Criteria:

  • Matched sibling donor or HLA-haploidentical relatives of the patient, including biological parents, siblings, or children, half-siblings, cousins or aunts and uncles
  • Weight is greater than 30 kg
  • Age 12 and 50 years
  • Ability to undergo phlebotomy
  • Cardiac, renal, pulmonary, and hepatic function within normal limits
  • Complete blood count (CBC) with differential and platelet count within normal limits, and CMP within normal limits as deemed acceptable by the Principal Investigator and provider evaluating donor.
  • The familial donors should be able complete the fitness evaluation to determine VO2max and peak cycling power and following successful completion of the donor evaluation, the patients willing to participate in the randomized trial will be enrolled.

DLI Recipient Exclusion Criteria:

  • Acute grade III-IV aGvHD or moderate/severe chronic GvHD.
  • Requiring immunosuppression therapy for treatment of GvHD.
  • Co-morbidities: AST/ALT greater than 5 x ULN; Bilirubin greater than 2 x ULN; Creatinine greater than 2 x ULN for age or creatinine clearance/GFR <40 ml/min/1.73m2; Pulmonary function: DLCO less than 40% of normal or O2 Sat less than 92%; Cardiac: left ventricular ejection fraction less than 35%; active infection; HIV positive; Karnofsky score (adults) less than 60% or Lansky score less than 50% (pediatrics)
  • Uncontrolled or severe bacterial, fungal or viral infection.
  • Positive serum or urine pregnancy test for girls post menarche or women of childbearing age.
  • Severe psychiatric illness or mental deficiency making compliance to treatment unlikely and/or informed consent impossible.
  • Any reason, at the investigator's discretion, that the participation of the patient in this protocol would not be in patient's best interest, or where the patient would be unable to adhere to the study requirements.

DLI Donor Exclusion Criteria:

  • Unable to perform graded exercise test
  • Cardiac or pulmonary disease restricting exercise
  • Positive anti-donor HLA antibody
  • Pregnant or lactating
  • Active infection
  • Positivity for HIV, hepatitis B (HBV), hepatitis C (HCV), human T-cell lymphotropic virus (HTLV-I/II)
  • Severe psychiatric illness or mental deficiency making compliance with donation unlikely and/or informed consent impossible.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Prophylactic Arm
Conduct the first-in-human, randomized clinical trial comparing prophylactic exercise mobilized donor lymphocyte infusion (pro-DLI-X) with standard (non exercise mobilized) prophylactic DLI (pro-DLI) for relapse prevention following allogeneic hematopoietic cell transplantation (alloHCT) in patients with myeloid or lymphoid malignancies.
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.
Other Names:
  • pro-DLI-X
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.
Other Names:
  • pro-DLI
Experimental: Therapeutic Arm
Compare therapeutic exercise mobilized donor lymphocyte infusion (t-DLI-X) with standard (non exercise mobilized) therapeutic DLI (t-DLI) in a randomized trial for patients with evidence of minimal residual disease (MRD+) or overt relapse post-alloHCT for myeloid or CD19-negative lymphoid malignancies.
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.
Other Names:
  • t-DLI-X
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prophylactic endpoint: Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS)
Time Frame: Assess between 1 to 3 years post HCT
Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS) is defined as survival without evidence of disease relapse or grade III-IV acute graft-versus-host-disease (aGvHD) or chronic graft-versus-host-disease (cGvHD) requiring systemic therapy. In essence, GRFS serves as a meaningful measure encompassing not only survival but quality of life. GRFS will be compared in patients randomized to pro-DLI-X versus standard pro-DLI control group.
Assess between 1 to 3 years post HCT
Therapeutic endpoint: Disease response to t-DLI versus t-DLI-X (relapse and GvHD rates as a composite endpoint)
Time Frame: Assess between 1-3 years post HCT
A parallel two-group design will be used to test whether the percent response to t-DLI-X (treatment) is different from the percent response to t-DLI (control).
Assess between 1-3 years post HCT

Collaborators and Investigators

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

Sponsor

University of Arizona

Investigators

  • Principal Investigator: Emmanuel Katsanis, MD, University of Arizona

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 (Estimated)

May 31, 2026

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 19, 2025

First Posted (Actual)

November 28, 2025

Study Record Updates

Last Update Posted (Actual)

April 7, 2026

Last Update Submitted That Met QC Criteria

April 1, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00006003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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