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

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ClinicalTrials.gov Identifier: NCT00987987
Recruitment Status : Completed
First Posted : October 1, 2009
Last Update Posted : January 24, 2011
Sponsor:
Collaborators:
Université Paris XII
Pierre and Marie Curie University
Information provided by:
Assistance Publique - Hôpitaux de Paris

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hematologic Neoplasms Relapse Procedure: donor lymphocyte infusion Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
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
Study Start Date : December 2005
Actual Primary Completion Date : December 2009
Actual Study Completion Date : December 2009
Arms and Interventions
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Arm Intervention/treatment
Experimental: 1
1
 Procedure: donor lymphocyte infusion
regulatory T cells depletion
Other Name: regulatory T cells depletion


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

Secondary Outcome Measures :
  1. The incidence of GVHD of any grade after dDLI [ Time Frame: during the 12 months ]
  2. The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy [ Time Frame: during the 12 months ]
  3. The survival and the survival without disease after dDLI [ Time Frame: during the 12 months ]

Eligibility Criteria
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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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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Responsible Party: Valérie Millul, Department Clinical Research of Developpement
ClinicalTrials.gov Identifier: NCT00987987     History of Changes
Other Study ID Numbers: P040441
First Posted: October 1, 2009    Key Record Dates
Last Update Posted: January 24, 2011
Last Verified: September 2009

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