Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion (ILD-Treg)

This study has been completed.

Sponsor:

Collaborators:

Université Paris XII

Pierre and Marie Curie University

Information provided by:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT00987987

First received: September 30, 2009

Last updated: January 21, 2011

Last verified: September 2009

History of Changes

Purpose

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.

Condition	Intervention	Phase
Hematologic Neoplasms Relapse	Procedure: donor lymphocyte infusion	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%. [ Time Frame: 4 weeks after dDLI ]

Secondary Outcome Measures:

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 ]


Enrollment:	21
Study Start Date:	December 2005
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 1	Procedure: donor lymphocyte infusion regulatory T cells depletion Other Name: regulatory T cells depletion

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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00987987

Locations


France
Hopital Henri Mondor
Créteil, France, 94000

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Université Paris XII

Pierre and Marie Curie University

Investigators


Principal Investigator:	Sébastien Maury, MD Ph	Assistance Publique - Hôpitaux de Paris

More Information

Publications:

Maury S, Lemoine FM, Hicheri Y, Rosenzwajg M, Badoual C, Cheraï M, Beaumont JL, Azar N, Dhedin N, Sirvent A, Buzyn A, Rubio MT, Vigouroux S, Montagne O, Bories D, Roudot-Thoraval F, Vernant JP, Cordonnier C, Klatzmann D, Cohen JL. CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Sci Transl Med. 2010 Jul 21;2(41):41ra52. doi: 10.1126/scitranslmed.3001302.


Responsible Party:	Valérie Millul, Department Clinical Research of Developpement
ClinicalTrials.gov Identifier:	NCT00987987 History of Changes
Other Study ID Numbers:	P040441
Study First Received:	September 30, 2009
Last Updated:	January 21, 2011

Keywords provided by Assistance Publique - Hôpitaux de Paris:


hematological malignancy allogeneic hematopoietic stem cell transplantation donor lymphocyte infusion antitumor immunotherapy	graft-versus-tumor effect regulatory T cells adult

Additional relevant MeSH terms:


Hematologic Neoplasms Neoplasms by Site Neoplasms Hematologic Diseases

ClinicalTrials.gov processed this record on August 17, 2017

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