Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study
18 Years
70 Years
Both
Hematologic Neoplasms, Relapse
Trial Information
Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study
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.
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).
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
Outcome Time Frame:
4 weeks after dDLI
Safety Issue:
Yes
Principal Investigator
Sébastien Maury, MD Ph
Investigator Role:
Principal Investigator
Investigator Affiliation:
Assistance Publique - Hôpitaux de Paris
Authority:
France: Ministry of Health
Study ID:
P040441
NCT ID:
NCT00987987
Start Date:
December 2005
Completion Date:
December 2009
Related Keywords:
- Hematologic Neoplasms
- Relapse
- hematological malignancy
- allogeneic hematopoietic stem cell transplantation
- donor lymphocyte infusion
- antitumor immunotherapy
- graft-versus-tumor effect
- regulatory T cells
- adult
- Neoplasms
- Hematologic Neoplasms
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