Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT06180499

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

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Hematological Malignancies Disease Attributes Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Neoplasms Neoplasms by Site Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Regulatory T Cell Depletion Relapse

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

T-reg depleted DLI

Drug

Treg depleted Donor Lymphocytes Infusion

Primary outcomes

  1. 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

Secondary outcomes

  1. Incidence of acute and/or chronic GVHD, with corresponding grades according to NIH and Glucksberg-Thomas scales

    Time frame: at 2 and 12 month

  2. 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

  3. Date of putative relapse/progression for estimation disease-free survival

    Time frame: at 2 and 12 month

  4. Number, causes and date of deaths

    Time frame: at 2 and 12 month

Study contacts

Contact information is provided by the study sponsor or research team.

elodie lemadre, M.Sc

CONTACT

[email protected]

01 44 84 17 34 ext. +33

sébastien maury, PhD

CONTACT

[email protected]

01.49.81.20.57 ext. +33

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: ILDTreg2

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Dec 22, 2023
Registry last updated
Feb 14, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.