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

NCT03236129 | Recruiting Phase 3 DMC

• 2 other identifiers: P1403032016-A00645-46
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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

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 clinical manifestations of GVHD, in the form of acute GVHD with grade ≥ 2 and/or extensive chronic. This parameter will take into account the competitive risk of death unrelated to the GVHD

  3 month after injection

Secondary Outcomes (3)

• Cumulative incidence of relapse, taking into account the competitive risk of death unrelated to relapse

  1 year after injection

• Relapse-free survival

  1 year after injection

• Overall survival

  1 year after injection

Study Arms (2)

Treg depleted DLI

EXPERIMENTAL

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

Procedure: T-reg depleted DLI

Unmanipulated DLI

ACTIVE COMPARATOR

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

Procedure: Standard DLI

Interventions

T-reg depleted DLI PROCEDURE

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

Treg depleted DLI

Standard DLI PROCEDURE

The patients in this arm benefit of a standard DLI.

Unmanipulated DLI

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Children and adults regardless of age or weight allograft for primary or secondary acute leukemia, MDS, lympho-proliferative syndrome (CLL, Myeloma, Lymphoma) or myelo-proliferative syndrome.
• Prior allogeneic HSCT (myeloablative or non-myeloablative conditioning) from a family donor geno-identical HLA or a volunteer donor HLA 10/10 or 9/10.
• Molecular, cytogenetic, cytological relapse regardless of the date after the transplant.
• Previous standard DLI should have brought a total dose of at least 5.10\^6 CD3 + / kg (donor HLA-geno idendique) or 2.10\^6 CD3 + / kg (voluntary donor) or 5.10\^5 CD3+/kg (donor haplo-idendique).
• Patient corresponding to the failure criteria of a previous standard DLI, defined for each type of hematological malignancies in the test model "DLI-Treg-1" after a delay of at least 30 days in the case of a progressive disease after DLI and at least 60 days in the case of stable disease (due to possible delayed responses after DLI).
• Patient consented to the study (the consent of both parents will be collected for minors)
• Patients insured by a social security system.
• Negative pregnancy test (β-HCG hormone) within the 7 days prior to enrollment

You may not qualify if:

• Presence of acute GVHD grade\> II or extensive chronic GVHD since the first DLI
• Patient receiving immunosuppressive therapy for the treatment of GVHD or other reason
• Impairment of liver function (transaminases\> 5 N or bilirubin\> 50 µM except Gilbert's disease) or renal function (creatinine clearance \<30 ml / min)
• OMS performance status \> 2
• Non controlled severe infection
• Patient under tutorship, curatorship or legal protection
• Being the initial HSC donor (HLA geno-identical family or haplo-identique or non-family HLA 10/10 or 9/10)
• Weight ≥20 kg authorizing the lymphapheresis
• Having no contra-indications for donating blood
• Absence of severe heart failure, unstable heart disease, uncontrolled hypertension, type 1 diabetes
• Negative serology for HIV1-2, HBV, HCV, HTLV 1 and VDRL/TPHA in the 30 days prior to apheresis. Negative viral genomics diagnosis is required for HIV, HBV and HCV
• Being informed of the study, and have given an oral non opposition

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

Related Publications (1)

• Maury S, Lemoine FM, Hicheri Y, Rosenzwajg M, Badoual C, Cherai M, Beaumont JL, Azar N, Dhedin N, Sirvent A, Buzyn A, Rubio MT, Vigouroux S, Montagne O, Bories D, Roudot-Thoraval F, Vernant JP, Cordonnier C, Klatzmann D, Cohen JL. CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Sci Transl Med. 2010 Jul 21;2(41):41ra52. doi: 10.1126/scitranslmed.3001302.

  PMID: 20650872 BACKGROUND

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

• Florence BEKCERICH, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Florence BECKERICH, MD

CONTACT

(0)1 49 81 20 57; florence.beckerich@aphp.fr

Sébastien MAURY, MD/ PhD

CONTACT

(0)1 49 81 20 57; sebastien.maury@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: August 1, 2017
• Study Start: February 22, 2018
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2026
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)