Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells (DLI-Boost)
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|ClinicalTrials.gov Identifier: NCT03236129|
Recruitment Status : Unknown
Verified November 2020 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was: Recruiting
First Posted : August 1, 2017
Last Update Posted : November 20, 2020
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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
|Condition or disease||Intervention/treatment||Phase|
|Hematological Malignancies Regulatory T Cell Depletion Relapse||Procedure: T-reg depleted DLI Procedure: Standard DLI||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells: A Confirmatory, Randomized, Double Blinded Trial|
|Actual Study Start Date :||February 22, 2018|
|Estimated Primary Completion Date :||February 2021|
|Estimated Study Completion Date :||February 2022|
Experimental: Treg depleted DLI
Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by Treg depleted (Donor Lymphocytes Infusion (DLI)
Procedure: T-reg depleted DLI
The patients in the experimental arm benefit of a DLI depleted from regulatory T lymphocytes
Active Comparator: Unmanipulated DLI
Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by a standard DLI (unmanipulated)
Procedure: Standard DLI
The patients in this arm benefit of a standard DLI.
- 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 [ Time Frame: 1 year after injection ]
- Cumulative incidence of relapse, taking into account the competitive risk of death unrelated to relapse [ Time Frame: 1 year after injection ]
- Relapse-free survival [ Time Frame: 1 year after injection ]
- Overall survival [ Time Frame: 1 year after injection ]
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|Ages Eligible for Study:||Child, Adult, Older Adult|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 5.106 CD3 + / kg (donor HLA-geno idendique) or 2.106 CD3 + / kg (voluntary donor).
- 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
- 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
Donor Inclusion Criteria
- Being the initial HSC donor (HLA geno-identical family 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03236129
|Contact: Florence BECKERICH, MD||(0)1 49 81 20 57 ext +firstname.lastname@example.org|
|Contact: Sébastien MAURY, MD/ PhD||(0)1 49 81 20 57 ext +email@example.com|
|Henri Mondor Hospital||Recruiting|
|Creteil, France, 94010|
|Contact: Damien VANHOYE, PhD (0)1 44 84 17 93 ext +33 firstname.lastname@example.org|
|Contact: Laetitia GREGOIRE, M. Sc (0)1 49 81 41 64 ext +33 Laetitia.email@example.com|
|Principal Investigator:||Florence BEKCERICH, MD||Assistance Publique - Hôpitaux de Paris|
|Responsible Party:||Assistance Publique - Hôpitaux de Paris|
|Other Study ID Numbers:||
2016-A00645-46 ( Other Identifier: IDRCB )
|First Posted:||August 1, 2017 Key Record Dates|
|Last Update Posted:||November 20, 2020|
|Last Verified:||November 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Regulatory T cells depletion
Neoplasms by Site