Prophylactic and Therapeutic DLI-X for Leukemia Relapse After HCT

NCT07254793 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00006003
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Exercise; Donor Lymphocyte Infusion; Allogeneic Hematopoietic Stem Cell Transplantation; Hematologic Malignancies; Matched Sibling Donor; Haploidentical; Hematopoietic Cell Transplantation; DLI-X

Outcome Measures

Primary Outcomes (2)

• Prophylactic endpoint: Graft-versus-Host Disease-Free, Relapse-Free Survival (GRFS)

  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)

  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

Study Arms (2)

Prophylactic Arm

EXPERIMENTAL

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; Biological: Standard Prophylactic DLI

Therapeutic Arm

EXPERIMENTAL

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; Biological: Standard Therapeutic DLI

Interventions

Exercise Mobilized Prophylactic DLI BIOLOGICAL

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.

Also known as: pro-DLI-X

Prophylactic Arm

Standard Prophylactic DLI BIOLOGICAL

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.

Also known as: pro-DLI

Prophylactic Arm

Exercise Mobilized Therapeutic DLI BIOLOGICAL

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.

Also known as: t-DLI-X

Therapeutic Arm

Standard Therapeutic DLI BIOLOGICAL

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.

Therapeutic Arm

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Motor Activity; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Behavior; Neoplasms by Site

Study Officials

• Emmanuel Katsanis, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michele Chu-Pilli

CONTACT

520-626-1183; chum@arizona.edu

UACC IIT

CONTACT

UACC-IIT@uacc.arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 28, 2025
• Study Start: February 28, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: November 28, 2025

Record last verified: 2025-11

Locations

US (1)