Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion (ILDTreg2)

Assistance Publique - Hôpitaux de Paris

Status and phase

Not yet enrolling

Phase 2

Phase 1

Conditions

Regulatory T Cell Depletion

Hematological Malignancies

Relapse

Treatments

Drug: T-reg depleted DLI

Study type

Interventional

Funder types

Other

Identifiers

NCT06180499

P120103

Details and patient eligibility

About

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.

Enrollment

27 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult patient (older than 18 years old without upper limit of age) diagnosed with leukemia, myelodysplasia, myeloproliferative disorder or lymphoproliferative disorder (CLL, myeloma, lymphoma)
Previous allogeneic HSCT from a matched sibling, haplo-identical or unrelated donor (any type of conditioning regimen)
Haematological relapse (molecular, cytogenetic or cytological) after HSCT
Patient refractory (no or partial response) to one or several previous standard unmanipulated DLI
Availability of cryopreserved lymphapheresis
No loss of chance by using of DLI rather than more incisive anti-tumor agents according to investigator appreciation
Written informed consent before any intervention necessary for the trial
Affiliation to a social security regime
Negative pregnancy test for women of childbearing age participating in the study
Effective contraceptive methods for men / women in line with the current CTFG recommendations version 1.1

Exclusion criteria

Acute grade ≥ II or moderate/severe chronic GVHD at the time of inclusion
Patient receiving immunosuppressive treatment for GVHD or any other reason
Creatinine clearance< 50 ml/min
Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 5.0 x upper limit of normal (ULN)
Serum total bilirubin > 50µM (expect for unconjugated hyperbilirubinemia due to Gilbert's disease)
Performance status ECOG>1
Severe infection according to CTCAE grading (grade>2)
Pregnant or lactating women
Patient under tutorship, curatorship or legal protection
Ongoing participation in another interventional research protocol within the same field of immune modulation (through cell therapy or not)
State medical aid