Hematological MalignanciesPhase 1/2ILDTreg2NCT06180499
Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion
A Phase 1/2 study testing T-reg depleted DLI in people with Hematological Malignancies and Regulatory T Cell Depletion, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Since the discovery that Treg suppress anti-tumor immune responses, inhibiting their function has become a major challenge for the development of efficient immunotherapy for cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancies, Regulatory T Cell Depletion, Relapse
- What is being tested?
- T-reg depleted DLI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- No sites listed yet
- Study dates
- Mar 2024to Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient (older than 18 years old without upper limit of age) diagnosed with leukemia, myelodysplasia, myeloproliferative disorder or lymphoproliferative disorder (CLL, myeloma, lymphoma)
- Previous allogeneic HSCT from a matched sibling, haplo-identical or unrelated donor (any type of conditioning regimen)
- Haematological relapse (molecular, cytogenetic or cytological) after HSCT
- Patient refractory (no or partial response) to one or several previous standard unmanipulated DLI
- Availability of cryopreserved lymphapheresis
- No loss of chance by using of DLI rather than more incisive anti-tumor agents according to investigator appreciation
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- Written informed consent before any intervention necessary for the trial
- Affiliation to a social security regime
- Negative pregnancy test for women of childbearing age participating in the study
- Effective contraceptive methods for men / women in line with the current CTFG recommendations version 1.1
Who cannot join
- Acute grade ≥ II or moderate/severe chronic GVHD at the time of inclusion
- Patient receiving immunosuppressive treatment for GVHD or any other reason
- Creatinine clearance< 50 ml/min
- Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 5.0 x upper limit of normal (ULN)
- Serum total bilirubin > 50µM (expect for unconjugated hyperbilirubinemia due to Gilbert's disease)
- Performance status ECOG>1
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- Severe infection according to CTCAE grading (grade>2)
- Pregnant or lactating women
- Patient under tutorship, curatorship or legal protection
- Ongoing participation in another interventional research protocol within the same field of immune modulation (through cell therapy or not)
- State medical aid
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Since the discovery that Treg suppress anti-tumor immune responses, inhibiting their function has become a major challenge for the development of efficient immunotherapy for cancer. In humans, we previously reported the positive results of a first clinical trial using Treg depletion for anti-tumor response amplification in the field of allogeneic hematopoietic stem cell transplantation (HSCT). The present project aims at developing this anti-tumor immunotherapeutic strategy in the same setting, i.e. donor lymphocyte infusion (DLI) for relapsing hematological malignancies after HSCT, using a new selection marker: CD127. The choice of this new strategy is supported by our results of a retrospective clinical study and pre-clinical data. Using human cells, this studies demonstrated, in vitro and in vivo in animal murine models, that Treg depletion through CD127 positive selection is much more efficient to improve allogeneic immune responses of donor T-cells as compared to the previous strategy using the CD25 marker.
- Being tested
- T-reg depleted 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 DLIDrug
Treg depleted Donor Lymphocytes Infusion
| Study group | Role | What they receive |
|---|---|---|
| T-reg depleted DLI | Experimental | Not described Receives: Drug: T-reg depleted DLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
cumulative incidence of GVHD in its acute grade ≥ II and/or severe chronic form (according Glucksberg-Thomas and NIH scales, respectively), and uncontrolled after a 14-day immunosuppressive course including steroids.
Composite criteria. In this evaluation, death from non-GVHD cause will be taken as a competitive event
Measured: occurring within the 2 months following d-DLI infusion
Secondary outcomes (4)
Incidence of acute and/or chronic GVHD, with corresponding grades according to NIH and Glucksberg-Thomas scales
Measured: at 2 and 12 month
Date of putative relapse/progression for estimation of cumulative incidence (taking into account the competitive risk of death not related to relapse)
Measured: at 2 and 12 month
Date of putative relapse/progression for estimation disease-free survival
Measured: at 2 and 12 month
Number, causes and date of deaths
Measured: at 2 and 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2023
- Study startMar 2024 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- elodie lemadre, M.Sc, Study chair, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06180499
- Sponsor's protocol ID
- P120103
- Acronym
- ILDTreg2
- Status last verified
- Feb 2024
- First submitted
- 12 Dec 2023
- Last updated
- 14 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion
- ClinicalTrials.gov ID
- NCT06180499
- Acronym / sponsor ID
- ILDTreg2 / P120103
- Keywords
- DLI, Regulatory T cells depletion, Hematological malignancies, Relapse
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2024 (estimated)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 22 Dec 2023 (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.
Since the discovery that Treg suppress anti-tumor immune responses, inhibiting their function has become a major challenge for the development of efficient immunotherapy for cancer. In humans, we previously reported the positive results of a first clinical trial using Treg depletion for anti-tumor response amplification in the field of allogeneic hematopoietic stem cell transplantation (HSCT). The present project aims at developing this anti-tumor immunotherapeutic strategy in the same setting, i.e. donor lymphocyte infusion (DLI) for relapsing hematological malignancies after HSCT, using a new selection marker: CD127. The choice of this new strategy is supported by our results of a retrospective clinical study and pre-clinical data. Using human cells, this studies demonstrated, in vitro and in vivo in animal murine models, that Treg depletion through CD127 positive selection is much more efficient to improve allogeneic immune responses of donor T-cells as compared to the previous strategy using the CD25 marker.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| T-reg depleted DLI | Experimental | Drug: T-reg depleted DLI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult patient (older than 18 years old without upper limit of age) diagnosed with leukemia, myelodysplasia, myeloproliferative disorder or lymphoproliferative disorder (CLL, myeloma, lymphoma)
- Previous allogeneic HSCT from a matched sibling, haplo-identical or unrelated donor (any type of conditioning regimen)
- Haematological relapse (molecular, cytogenetic or cytological) after HSCT
- Patient refractory (no or partial response) to one or several previous standard unmanipulated DLI
- Availability of cryopreserved lymphapheresis
Key exclusion criteria (11 listed)
- Acute grade ≥ II or moderate/severe chronic GVHD at the time of inclusion
- Patient receiving immunosuppressive treatment for GVHD or any other reason
- Creatinine clearance< 50 ml/min
- Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 5.0 x upper limit of normal (ULN)
- Serum total bilirubin > 50µM (expect for unconjugated hyperbilirubinemia due to Gilbert's disease)
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 DLITreg depleted Donor Lymphocytes Infusion | Drug | T-reg depleted DLI |
Primary outcome
cumulative incidence of GVHD in its acute grade ≥ II and/or severe chronic form (according Glucksberg-Thomas and NIH scales, respectively), and uncontrolled after a 14-day immunosuppressive course including steroids.
Time frame: occurring within the 2 months following d-DLI infusion
Composite criteria. In this evaluation, death from non-GVHD cause will be taken as a competitive event
4 secondary outcomes
Incidence of acute and/or chronic GVHD, with corresponding grades according to NIH and Glucksberg-Thomas scales
Time frame: at 2 and 12 month
Date of putative relapse/progression for estimation of cumulative incidence (taking into account the competitive risk of death not related to relapse)
Time frame: at 2 and 12 month
Date of putative relapse/progression for estimation disease-free survival
Time frame: at 2 and 12 month
Number, causes and date of deaths
Time frame: at 2 and 12 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2024.
- 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.
elodie lemadre, M.Sc study chair
APHP
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing T-reg depleted DLI in people with Hematological Malignancies and Regulatory T Cell Depletion, run by Assistance Publique - Hôpitaux de Paris.
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 10 inclusion and 11 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: opening soon, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact sébastien maury, PhD (01.49.81.20.57 ext. +33, sebastien.maury@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 GVHD in its acute grade ≥ II and/or severe chronic form (according Glucksberg-Thomas and NIH scales, respectively), and uncontrolled after a 14-day immunosuppressive course including steroids. (time frame: occurring within the 2 months following d-DLI infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Feb 2024.