Hematologic NeoplasmsPhase 1/2ILD-TregNCT00987987
Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion
A Phase 1/2 study testing donor lymphocyte infusion in people with Hematologic Neoplasms and Relapse, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The investigators have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hematologic Neoplasms, Relapse
- What is being tested?
- donor lymphocyte infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2005to Dec 2009
- Phase
- Phase 1/2
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hematological malignancy except chronic myeloid leukaemia.
- Previous allogeneic hematopoietic stem cell transplantation.
- Relapse diagnosed at the molecular, cytogenetic, or cytological level.
- Failure of a previous stdILD or inclusion in first intention if progressive disease.
- Age > 18 years and < 70 years at the time of inclusion.
- Performance status considered on the score ECOG < 2.
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- Life expectation 1-month-old superior.
- Signed written informed consent.
- Negative HCG in the 7 days preceding the inclusion for women in age of procreation.
- Membership of the French national insurance.
Who cannot join
- Chronic myeloid leukemia
- Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.
- Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
- Dysfunction of liver (ALAT/ASAT > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study
The investigators have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. The investigators thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.
Read the detailed description
We have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. We thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.
dDLI is administered after failure of 1 or several previous stdDLI of at least 107 CD3+ cells/kg, defined after a minimal follow-up of 2 months after the last injection. The absence of previous clinical manifestations of GVHD is required to be included. To prepare dDLI, CD25+ Treg are depleted from donor leukaphereses using anti-CD25 magnetic microbeads and a CliniMACS device (MYLTENYI). In order to evidence the potential effect of dDLI, the dDLI cell dose is adjusted to be below or equal to the maximal cell dose previously received in stdDLI. No comparison is planned in the analysis.
- Conditions
- Hematologic Neoplasms, Relapse
- Being tested
- donor lymphocyte infusion
- Keywords
- hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, regulatory T cells, adult
- 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.
donor lymphocyte infusionProcedure or surgery
Also called regulatory T cells depletion
regulatory T cells depletion
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 1 Receives: Procedure: donor lymphocyte infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
Measured: 4 weeks after dDLI
Secondary outcomes (3)
The incidence of GVHD of any grade after dDLI
Measured: during the 12 months
The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy
Measured: during the 12 months
The survival and the survival without disease after dDLI
Measured: during the 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2009 (estimated)
- Study startDec 2005
- Primary completionDec 2009
- Study completionDec 2009
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 Hematologic NeoplasmsStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Université Paris XII, Pierre and Marie Curie University
- Investigators
- Sébastien Maury, MD Ph, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987987
- Sponsor's protocol ID
- P040441
- Acronym
- ILD-Treg
- Status last verified
- Sep 2009
- First submitted
- 30 Sep 2009
- Last updated
- 24 Jan 2011
- Results posted
- No
- Data monitoring committee
- 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 24 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study
- ClinicalTrials.gov ID
- NCT00987987
- Acronym / sponsor ID
- ILD-Treg / P040441
- Conditions
- Hematologic Neoplasms, Relapse
- Keywords
- hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, regulatory T cells, adult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Université Paris XII, Pierre and Marie Curie University
- Study start
- Dec 2005
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 1 Oct 2009 (estimated)
- 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 that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. The investigators thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.
Detailed description
We have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. We thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.
dDLI is administered after failure of 1 or several previous stdDLI of at least 107 CD3+ cells/kg, defined after a minimal follow-up of 2 months after the last injection. The absence of previous clinical manifestations of GVHD is required to be included. To prepare dDLI, CD25+ Treg are depleted from donor leukaphereses using anti-CD25 magnetic microbeads and a CliniMACS device (MYLTENYI). In order to evidence the potential effect of dDLI, the dDLI cell dose is adjusted to be below or equal to the maximal cell dose previously received in stdDLI. No comparison is planned in the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: donor lymphocyte infusion1 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Hematological malignancy except chronic myeloid leukaemia.
- Previous allogeneic hematopoietic stem cell transplantation.
- Relapse diagnosed at the molecular, cytogenetic, or cytological level.
- Failure of a previous stdILD or inclusion in first intention if progressive disease.
- Age > 18 years and < 70 years at the time of inclusion.
Key exclusion criteria (4 listed)
- Chronic myeloid leukemia
- Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.
- Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
- Dysfunction of liver (ALAT/ASAT > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).
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 |
|---|---|---|
| donor lymphocyte infusionAlso: regulatory T cells depletionregulatory T cells depletion | Procedure or surgery | 1 |
Primary outcome
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
Time frame: 4 weeks after dDLI
3 secondary outcomes
The incidence of GVHD of any grade after dDLI
Time frame: during the 12 months
The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy
Time frame: during the 12 months
The survival and the survival without disease after dDLI
Time frame: during the 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2011.
- Results publication: 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.
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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.
Sébastien Maury, MD Ph 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 1/2 study testing donor lymphocyte infusion in people with Hematologic Neoplasms and Relapse, 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 10 inclusion and 4 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: finished, as of the sponsor's last update on 24 Jan 2011. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%. (time frame: 4 weeks after dDLI). 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 NCT00987987, 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 24 Jan 2011.