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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by Treg depleted (Donor Lymphocytes Infusion (DLI)

Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by a standard DLI (unmanipulated)

The patients in the experimental arm benefit of a DLI depleted from regulatory T lymphocytes

T-reg depleted DLI

The patients in this arm benefit of a standard DLI.

Standard DLI

Florence BECKERICH, MD

Sébastien MAURY, MD/ PhD

Damien VANHOYE, PhD

Laetitia GREGOIRE, M. Sc

Florence BEKCERICH, MD

The investigators have previously shown the absence of toxicity of Treg-depleted-DLI and the possibility to triggering alloreactivity (GVHD/GVT) in relapsing patients dealing with hematological malignancies who had never shown any signs of GVHD after transplant or after one or more DLI.

The Investigators, we plan to demonstrate the benefit of Treg-depleted DLI as compared to the reference treatment of relapse in hematological malignancies after allogeneic HSCT which is currently based on standard DLI

This clinical trial is designed to demonstrate the benefit of Treg-depleted DLI as compared to the reference treatment of relapse in hematological malignancies after allogeneic HSCT which is currently based on standard DLI.

Patients who have never shown any signs of GVHD and for which one (or more) unmanipulated DLI have been ineffective. Those patients will receive a subsequent DLI, which will be either unmanipulated (control arm) or Treg depleted (experimental arm) after a randomization. In both cases, the second DLI will be immediately preceded by a lymphodepleting treatment based on cyclophosphamide and fludarabine association.

Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells

Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells: A Confirmatory, Randomized, Double Blinded Trial

Assistance Publique - Hôpitaux de Paris

sébastien maury, PhD

elodie lemadre, M.Sc

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.

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

Composite criteria. In this evaluation, death from non-GVHD cause will be taken as a competitive event

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells	NCT03236129	Hematological M... Regulatory T Ce... Relapse	T-reg depleted ... Standard DLI	-	Assistance Publique - Hôpitaux de Paris
Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion	NCT06180499	Hematological M... Regulatory T Ce... Relapse	T-reg depleted ...	18 Years -	Assistance Publique - Hôpitaux de Paris
Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells	NCT03236129	Hematological M... Regulatory T Ce... Relapse	T-reg depleted ... Standard DLI	-	Assistance Publique - Hôpitaux de Paris

Spots Global Cancer Trial Database for regulatory t cell depletion