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

September 30, 2009
January 21, 2011
December 2005
December 2009   (final data collection date for primary outcome measure)
Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%. [ Time Frame: 4 weeks after dDLI ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00987987 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion
Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hematologic Neoplasms
  • Relapse
Procedure: donor lymphocyte infusion
regulatory T cells depletion
Other Name: regulatory T cells depletion
Experimental: 1
1
Intervention: Procedure: donor lymphocyte infusion
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
December 2009
December 2009   (final data collection date for primary outcome measure)

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).
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00987987
P040441
No
Valérie Millul, Department Clinical Research of Developpement
Assistance Publique - Hôpitaux de Paris
  • Université Paris XII
  • Université Paris VI
Principal Investigator: Sébastien Maury, MD Ph Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP