Innate Donor Effector Allogeneic Lymphocyte Infusion After Stem Cell Transplantation: the IDEAL Trial

NCT05686538 | Recruiting Phase 2

• 1 other identifier: Protocol VIP14.0.11
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The curative principle behind allogeneic hematopoietic stem cell transplantation (HSCT) is eradication of the malignant cells of the patient (recipient) by donor graft cells, a process termed graft-versus-leukemia (GVL) effect. GVL is traditionally mediated by donor αβ T cells in an immunological process driven by genetical differences between individuals, i.e. an allogeneic response. For this reason, αβ T cells also cause an unwanted and dangerous complication of HSCT called graft-versus-host disease (GVHD) in which healthy recipient cells are targeted by donor cells with great risk of morbidity and mortality to the patient. In addition to αβ T cells, other cells from the donor stem cell graft, termed innate effector lymphocytes, can contribute to the GVL effect. These are termed natural killer (NK) cells and T-cell receptor (TCR) γδ cells, the latter being a subset of T cells. NK and TCR γδ cells can recognize and eliminate leukemic cells in a direct tumor response independent of conventional allogeneicity. Therefore, opposite αβ T cells, innate effector lymphocytes cells can mediate GVL but are not likely to cause GVHD. The main indications for HSCT in adults are acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Approximately 50% of AML/MDS transplant patients experience significant acute GVHD and 30% experience relapse of the malignant disease. Prospective clinical studies from the research group of the investigators have shown that patients with high doses of innate lymphocytes in stem cell grafts and during early immune reconstitution after HSCT have a reduced risk of both GVHD and relapse. The aim of this clinical trial is therefore to administer innate donor lymphocyte infusion (iDLI) enriched in NK and TCR γδ cells and depleted of αβ T cells in patients early after HSCT. By improving the HSCT procedure with iDLI cell therapy the scope is less GVHD and less relapse of the malignant disease and thereby improved survival and life quality in AML/MDS patients.

Conditions

AML/MDS

Keywords

allogeneic stem cell transplantation; NK cells; TCR gamma delta cells; DLI

Outcome Measures

Primary Outcomes (2)

• Relapse-free survival

  Relapse-free survival

  1 year from transplantation

• aGVHD

  Acute graft-versus-host-disease grade 2-4

  100 days from transplantation

Secondary Outcomes (3)

• iDLI dose

  14 days from transplantation

• iDLI phenotype

  14 days from transplantation

• Neutrophil engraftment

  100 days from transplantation

Other Outcomes (4)

• Stem cell graft dose

  During procedure

• Stem cell graft phenotype

  During procedure

• Immune reconstitution cell doncentrations

  14-91 days from transplantation

Study Arms (2)

Innate donor lymphocyte infusion (iDLI)

EXPERIMENTAL

TCRab/CD19 depleted DLI day 14 after routine allogeneic stem cell transplantation

Other: iDLI

Standard of care

NO INTERVENTION

Routine allogeneic stem cell transplantation

Interventions

iDLI OTHER

TCRab/CD19 depleted DLI 14 days after allogeneic stem cell transplantation. Targeted cell doses: \>10e7 NK cells/kg and \>10e6 TCRgd cells/kg

Also known as: innate donor lymphocyte infusion (iDLI)

Innate donor lymphocyte infusion (iDLI)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnoses: AML, MDS
• Age: ≥18 years
• Graft type: PBSC
• Donor: ≥18 years
• Informed consent from both donor and recipient

You may not qualify if:

• Donors with need for central venous access for the leukapheresis procedure

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Study Officials

• Lia Minculescu, MD, PhD

  Department of Clinical Immunology, Rigshospitalet, Copenhagen.

  STUDY DIRECTOR

Central Study Contacts

Lia Minculescu, MD, PhD

CONTACT

+4535457958; lia.minculescu@regionh.dk

Henrik Sengelov, Professor

CONTACT

+4535458373; henrik.sengeloev@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Genetic randomization. Patients with related donors are included in the intervention group. Patients with unrelated donors are included in the control group.

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 17, 2023
• Study Start: January 1, 2022
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)