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

NCT ID: NCT03236129

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-22

Study Completion Date

2026-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This clinical trial is designed 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.

Patients who have never shown any signs of GVHD and for which one (or more) unmanipulated DLI have been ineffective. Those patients will receive a subsequent DLI, which will be either unmanipulated (control arm) or Treg depleted (experimental arm) after a randomization. In both cases, the second DLI will be immediately preceded by a lymphodepleting treatment based on cyclophosphamide and fludarabine association.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Hematological Malignancies Regulatory T Cell Depletion Relapse

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

DLI Regulatory T cells depletion Hematological malignancies Relapse

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treg depleted DLI

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

Group Type EXPERIMENTAL

T-reg depleted DLI

Intervention Type PROCEDURE

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

Unmanipulated DLI

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

Group Type ACTIVE_COMPARATOR

Standard DLI

Intervention Type PROCEDURE

The patients in this arm benefit of a standard DLI.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

T-reg depleted DLI

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

Intervention Type PROCEDURE

Standard DLI

The patients in this arm benefit of a standard DLI.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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


* 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

Exclusion Criteria

* 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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Florence BEKCERICH, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Henri Mondor Hospital

Créteil, , France

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Florence BECKERICH, MD

Role: CONTACT

Phone: (0)1 49 81 20 57

Email: [email protected]

Sébastien MAURY, MD/ PhD

Role: CONTACT

Phone: (0)1 49 81 20 57

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Damien VANHOYE, PhD

Role: primary

Laetitia GREGOIRE, M. Sc

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 20650872 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2016-A00645-46

Identifier Type: OTHER

Identifier Source: secondary_id

P140303

Identifier Type: -

Identifier Source: org_study_id