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Not yet recruiting NCT06180499

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

Phase I / Phase II Interventional Hematological Malignancies Regulatory T Cell Depletion Relapse

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: T-reg depleted DLI.
Who it may be relevant to
Registry conditions: Hematological Malignancies, Regulatory T Cell Depletion, Relapse. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Center list to be confirmed — check the primary protocol.
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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.

Interventions

  • Drug T-reg depleted DLI
    Treg depleted Donor Lymphocytes Infusion

Primary outcome measures

  • 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]
Secondary outcome measures (4)
  • Incidence of acute and/or chronic GVHD, with corresponding grades according to NIH and Glucksberg-Thomas scales [Time frame: at 2 and 12 month]
  • Date of putative relapse/progression for estimation of cumulative incidence (taking into account the competitive risk of death not related to relapse) [Time frame: at 2 and 12 month]
  • Date of putative relapse/progression for estimation disease-free survival [Time frame: at 2 and 12 month]
  • Number, causes and date of deaths [Time frame: at 2 and 12 month]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06180499 · P120103

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗