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Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study

Phase 1/Phase 2
18 Years
70 Years
Not Enrolling
Hematologic Neoplasms, Relapse

Thank you

Trial Information

Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study

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.

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

- Dysfunction of liver (ALAT/ASAT > 5 N, or bilirubin > 50 µM), or of the renal
function (creatinine clearance < 30 ml / min).

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.

Outcome Time Frame:

4 weeks after dDLI

Safety Issue:


Principal Investigator

Sébastien Maury, MD Ph

Investigator Role:

Principal Investigator

Investigator Affiliation:

Assistance Publique - Hôpitaux de Paris


France: Ministry of Health

Study ID:




Start Date:

December 2005

Completion Date:

December 2009

Related Keywords:

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