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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
Université Paris VI
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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The incidence of GVHD of any grade after dDLI [ Time Frame: during the 12 months ] [ Designated as safety issue: No ]
  • The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy [ Time Frame: during the 12 months ] [ Designated as safety issue: No ]
  • The survival and the survival without disease after dDLI [ Time Frame: during the 12 months ] [ Designated as safety issue: Yes ]
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
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Université Paris VI
Investigators
Principal Investigator: Sébastien Maury, MD Ph Assistance Publique - Hôpitaux de Paris
  More Information

Publications:

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
Health Authority: France: Ministry of Health

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
Hematologic Diseases
Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on February 27, 2015