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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.
4 weeks after dDLI
Sébastien Maury, MD Ph
Assistance Publique - Hôpitaux de Paris
France: Ministry of Health