Hematologic Neoplasms, Relapse
Conditions
Keywords
hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, regulatory T cells, adult
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.
Interventions
PROCEDUREdonor lymphocyte infusion
regulatory T cells depletion
Sponsors
Université Paris XII
Pierre and Marie Curie University
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of severe GHVD (grade >II) following dDLI should be inferior to 40%. | 4 weeks after dDLI |
Secondary
| Measure | Time frame |
|---|---|
| The incidence of GVHD of any grade after dDLI | during the 12 months |
| The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy | during the 12 months |
| The survival and the survival without disease after dDLI | during the 12 months |
Countries
France
Outcome results
None listed