Hematological MalignanciesPhase 3DLI-BoostNCT03236129
Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells
A Phase 3 study testing T-reg depleted DLI and Standard DLI in people with Hematological Malignancies and Regulatory T Cell Depletion, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hematological Malignancies, Regulatory T Cell Depletion, Relapse
- What is being tested?
- T-reg depleted DLI and Standard DLI
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteFrance
- Study dates
- 22 Feb 2018to Feb 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- Donor Inclusion Criteria
- 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
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Henri Mondor Hospital
Créteil, 94010
Damien VANHOYE, PhD, (0)1 44 84 17 93 ext. +33, damien.vanhoye@drc.aphp.fr
Laetitia GREGOIRE, M. Sc, (0)1 49 81 41 64 ext. +33, Laetitia.gregoire@aphp.fr
About this study
Official title: Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells: A Confirmatory, Randomized, Double Blinded Trial
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
Read the 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.
- Being tested
- T-reg depleted DLI, Standard DLI
- Keywords
- DLI, Regulatory T cells depletion, Hematological malignancies, Relapse
- Medical subject headings
- Hematologic Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-reg depleted DLIProcedure or surgery
The patients in the experimental arm benefit of a DLI depleted from regulatory T lymphocytes
Standard DLIProcedure or surgery
The patients in this arm benefit of a standard DLI.
| Study group | Role | What they receive |
|---|---|---|
| Treg depleted DLI | Experimental | Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by Treg depleted (Donor Lymphocytes Infusion (DLI) Receives: 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) Receives: Procedure: Standard DLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 month after injection
Secondary outcomes (3)
Cumulative incidence of relapse, taking into account the competitive risk of death unrelated to relapse
Measured: 1 year after injection
Relapse-free survival
Measured: 1 year after injection
Overall survival
Measured: 1 year after injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2017
- Study start22 Feb 2018
- Primary completionFeb 2025 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematological MalignanciesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Florence BEKCERICH, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236129
- Sponsor's protocol ID
- P140303
- Other IDs
- 2016-A00645-46
- Acronym
- DLI-Boost
- Status last verified
- Dec 2023
- First submitted
- 5 Jul 2017
- Last updated
- 18 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 20650872
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells: A Confirmatory, Randomized, Double Blinded Trial
- ClinicalTrials.gov ID
- NCT03236129
- Acronym / sponsor ID
- DLI-Boost / P140303
- Keywords
- DLI, Regulatory T cells depletion, Hematological malignancies, Relapse
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 22 Feb 2018 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 1 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treg depleted DLI | Experimental | Procedure: T-reg depleted DLIPatients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by Treg depleted (Donor Lymphocytes Infusion (DLI) |
| Unmanipulated DLI | Active comparator | Procedure: Standard DLIPatients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by a standard DLI (unmanipulated) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| T-reg depleted DLIThe patients in the experimental arm benefit of a DLI depleted from regulatory T lymphocytes | Procedure or surgery | Treg depleted DLI |
| Standard DLIThe patients in this arm benefit of a standard DLI. | Procedure or surgery | Unmanipulated DLI |
Primary outcome
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: 3 month after injection
3 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2023.
- Background: PubMed 20650872Maury 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florence BEKCERICH, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing T-reg depleted DLI and Standard DLI in people with Hematological Malignancies and Regulatory T Cell Depletion, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Florence BECKERICH, MD ((0)1 49 81 20 57 ext. +33, florence.beckerich@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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: 3 month after injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03236129, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2023.