Back to resultsAmplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion (ILD-Treg)
Primary Purpose
Hematologic Neoplasms, Relapse
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
donor lymphocyte infusion
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Neoplasms focused on measuring hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, regulatory T cells, adult
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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).
Sites / Locations
- Hopital Henri Mondor
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
1
Outcomes
Primary Outcome Measures
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
Secondary Outcome Measures
The incidence of GVHD of any grade after dDLI
The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy
The survival and the survival without disease after dDLI
Full Information
NCT ID
NCT00987987
First Posted
September 30, 2009
Last Updated
January 21, 2011
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Université Paris XII, Pierre and Marie Curie University
1. Study Identification
Unique Protocol Identification Number
NCT00987987
Brief Title
Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion
Acronym
ILD-Treg
Official Title
Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Université Paris XII, Pierre and Marie Curie University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Neoplasms, Relapse
Keywords
hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, regulatory T cells, adult
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
1
Intervention Type
Procedure
Intervention Name(s)
donor lymphocyte infusion
Other Intervention Name(s)
regulatory T cells depletion
Intervention Description
regulatory T cells depletion
Primary Outcome Measure Information:
Title
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
Time Frame
4 weeks after dDLI
Secondary Outcome Measure Information:
Title
The incidence of GVHD of any grade after dDLI
Time Frame
during the 12 months
Title
The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy
Time Frame
during the 12 months
Title
The survival and the survival without disease after dDLI
Time Frame
during the 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
Exclusion Criteria:
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sébastien Maury, MD Ph
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Henri Mondor
City
Créteil
ZIP/Postal Code
94000
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
20650872
Citation
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.
Results Reference
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Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion
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