Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells (DLI-Boost)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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


Condition or disease Intervention/treatment Phase
Hematological Malignancies Regulatory T Cell Depletion Relapse Procedure: T-reg depleted DLI Procedure: Standard DLI Phase 3

Detailed Description:

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 [ Time Frame: 1 year after injection ]

Secondary Outcome Measures :
  1. Cumulative incidence of relapse, taking into account the competitive risk of death unrelated to relapse [ Time Frame: 1 year after injection ]
  2. Relapse-free survival [ Time Frame: 1 year after injection ]
  3. Overall survival [ Time Frame: 1 year after injection ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 5.106 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

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

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Florence BECKERICH, MD (0)1 49 81 20 57 ext +33 florence.beckerich@aphp.fr
Contact: Sébastien MAURY, MD/ PhD (0)1 49 81 20 57 ext +33 sebastien.maury@aphp.fr

Locations
Layout table for location information
France
Henri Mondor Hospital Recruiting
Creteil, France, 94010
Contact: Damien VANHOYE, PhD    (0)1 44 84 17 93 ext +33    damien.vanhoye@drc.aphp.fr   
Contact: Laetitia GREGOIRE, M. Sc    (0)1 49 81 41 64 ext +33    Laetitia.gregoire@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Layout table for investigator information
Principal Investigator: Florence BEKCERICH, MD Assistance Publique - Hôpitaux de Paris
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03236129    
Other Study ID Numbers: P140303
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
DLI
Regulatory T cells depletion
Hematological malignancies
Relapse
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Hematologic Neoplasms
Recurrence
Disease Attributes
 Pathologic Processes
Neoplasms by Site
Hematologic Diseases