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

Phase 1

Completed

• Conditions: Hematologic Neoplasms; Relapse
• Interventions: Procedure: donor lymphocyte infusion

• Registration Number: NCT00987987
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study Start: 2005-12
• Status Verified: 2009-09
• Study First Submitted: 2009-09-30
• Study First Submitted QC: 2009-09-30
• Study First Posted: 2009-10-01
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Last Update Submitted: 2011-01-21
• Last Update Posted: 2011-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	donor lymphocyte infusion	1

Primary Outcome Measures

Name	Time	Method
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.	4 weeks after dDLI

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hopital Henri Mondor; 🇫🇷 Créteil, France