Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion

Assistance Publique - Hôpitaux de Paris21 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.

Time frame: 4 weeks after dDLI

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

Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes