NCT06180499: ILDTreg2

Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion

Not yet recruiting Phase 1/Phase 2 Last updated 12 February 2024

What this trial tests

Phase 1/Phase 2 trial testing T-reg depleted DLI in Hematological Malignancies in 27 participants. Not yet recruiting.

Timeline

1 March 2024

Primary endpoint
1 November 2028

1 September 2029

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 1/Phase 2
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	27
Start date	1 March 2024
Primary completion	1 November 2028
Estimated completion	1 September 2029

Drugs / interventions tested

• T-reg depleted DLI — full drug profile →

Conditions studied

• Hematological Malignancies — all drugs for Hematological Malignancies →
• Regulatory T Cell Depletion — all drugs for Regulatory T Cell Depletion →
• Relapse — all drugs for Relapse →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Hematological Malignancies or Regulatory T Cell Depletion. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• cumulative incidence of GVHD in its acute grade ≥ II and/or severe chronic form (according Glucksberg-Thomas and NIH scales, respectively), and uncontrolled after a 14-day immunosuppressive course including steroids.
  Time frame: occurring within the 2 months following d-DLI infusion
  Composite criteria. In this evaluation, death from non-GVHD cause will be taken as a competitive event

Sponsor's own description

Since the discovery that Treg suppress anti-tumor immune responses, inhibiting their function has become a major challenge for the development of efficient immunotherapy for cancer. In humans, we previously reported the positive results of a first clinical trial using Treg depletion for anti-tumor response amplification in the field of allogeneic hematopoietic stem cell transplantation (HSCT). The present project aims at developing this anti-tumor immunotherapeutic strategy in the same setting, i.e. donor lymphocyte infusion (DLI) for relapsing hematological malignancies after HSCT, using a new selection marker: CD127. The choice of this new strategy is supported by our results of a retrospective clinical study and pre-clinical data. Using human cells, this studies demonstrated, in vitro and in vivo in animal murine models, that Treg depletion through CD127 positive selection is much more efficient to improve allogeneic immune responses of donor T-cells as compared to the previous strategy using the CD25 marker.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.
   Wang L, Liang Y, Zhao C, Ma P, et al · · 2025 · cited 26× · PMID 41087343 · DOI 10.1038/s41392-025-02326-4
2. Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.
   Yue Y, Ren Y, Lu C, Li P, et al · · 2024 · cited 15× · PMID 39144146 · DOI 10.3389/fimmu.2024.1444533