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

NCT06180499 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: P120103
• Study Type: interventional
• Target: 27
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hematological Malignancies; Regulatory T Cell Depletion; Relapse

Keywords

DLI; Regulatory T cells depletion; Hematological malignancies; Relapse

Outcome Measures

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.

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

  occurring within the 2 months following d-DLI infusion

Secondary Outcomes (4)

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

  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)

  at 2 and 12 month

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

  at 2 and 12 month

• Number, causes and date of deaths

  at 2 and 12 month

Study Arms (1)

T-reg depleted DLI

EXPERIMENTAL

Drug: T-reg depleted DLI

Interventions

T-reg depleted DLI DRUG

Treg depleted Donor Lymphocytes Infusion

T-reg depleted DLI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Hematologic Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• elodie lemadre, M.Sc

  APHP

  STUDY CHAIR

Central Study Contacts

sébastien maury, PhD

CONTACT

01.49.81.20.57; sebastien.maury@aphp.fr

elodie lemadre, M.Sc

CONTACT

01 44 84 17 34; elodie.lemadre@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: December 22, 2023
• Study Start: March 1, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: February 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share