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Naive T-Cell Depleted Donor Lymphocyte Infusion Following Allogeneic Stem Cell Transplantation

Phase 1
18 Years
Open (Enrolling)
Hematological Malignancies

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Trial Information

Naive T-Cell Depleted Donor Lymphocyte Infusion Following Allogeneic Stem Cell Transplantation

Allogeneic stem cell transplantation (SCT) offers the hope of cure for a wide variety of
hematologic malignancies. Mature donor T-cells play a critical role in the success or
failure of this procedure. A subset of donor T-cells mediates graft-versus-host disease
(GvHD). Other subsets provide the foundation for immune recovery. Pan-depletion of mature
donor T-cells is an obligate step in haploidentical allogeneic stem cell transplantation.
Without this step, the recipient would succumb to lethal acute GVHD. We have had extensive
experience with in-vivo donor (and recipient) T-cell depletion using alemtuzumab as part of
the bone marrow conditioning regimen. We and others have also used anti-thymocyte globulin
for the same purpose. Pan-depletion of T-cells eliminates GvHD but significantly increases
the risks of tumor relapse and opportunistic infections. A delayed donor lymphocyte
infusion augments immune recovery and the graft versus tumor response, but it comes at the
risk of inducing lethal GvHD. This is particularly problematic when the donor and recipient
are HLA-discordant. Thus the major challenge in allogeneic stem cell transplantation is
determining how to maximally exploit the beneficial effects mediated by T-cells without
causing GvHD. This challenge could be overcome by selectively depleting the population of
donor T-cells responsible for eliciting the GvHD response. We have been interested in
selecting T-cells based on their naïve or memory phenotype to understand the contribution of
each of these cells to the pathogenesis of GvHD. Naïve T-cells (CD62L+ or CD45RA+) are
T-cells that have not encountered antigens specific for their T-cell receptor. Memory
T-cells (CD62L- or CD62L+ or CD45RA-) are T-cells that have previously been exposed to their
corresponding cognate antigens. If a donor has not encountered host alloantigens,
GvHD-inducing host-reactive T-cells should be contained in the naïve T-cell compartment. In
contrast, all the memory phenotype cells should not recognize host alloantigens. If this
hypothesis is correct as suggested by several published studies, CD62L- T-cells, which are
devoid of naïve T-cells and represent a subset of memory T-cells, should not be able to
induce GvHD. The study hypothesis is depletion of naïve T-cells from the donor lymphocyte
inoculum will abrogate GVHD while providing immunocompetent memory T-cells to affect an
anti-infection and a graft versus tumor response. In this study, we will determine the
maximum tolerated dose of a naïve T-cell depleted donor lymphocyte infusion given to
patients following HLA-matched and HLA-mismatched, allogeneic stem cell transplantation. We
will assess the GVHD-inducing potential of this donor lymphocyte infusion and further
monitor the impact that this DLI will have on post-transplant immune recovery.

Inclusion Criteria:

- Patients who have undergone an alemtuzumab or thymoglobulin-containing allogeneic
transplant procedure from a 3-5/6 HLA matched family donor, HLA-identical family
donor, or an 8/8 HLA-matched unrelated donor.

- At least 60 days from day of transplantation.

- Karnofsky performance status 50-100%.

- Donor myeloid engraftment (from peripheral blood or bone marrow) of at least 40%
documented ≤ 60 days from protocol therapy.

- No active acute GvHD ≥ grade II.

- Prednisone (or equivalent corticosteroid) dose ≤ 20mg, daily mycophenolate mofetil
dose ≤2000mg/d and cyclosporine/tacrolimus at ≤ therapeutic blood trough levels.

- No change in dosing of immunosuppressive agents 2 weeks before the naïve T-cell
depleted donor lymphocyte infusion.

- A commitment not to electively taper for a minimum of 60 days, the immunosuppressive
medications ongoing at time of naïve T-cell depleted donor lymphocyte infusion.

- No extensive chronic GvHD.

- Age ≥ 18 years of age.

Exclusion Criteria:

- Pregnant or lactating women.

- Patients with other major medical or psychiatric illnesses, which the treating
physician feels, could seriously compromise tolerance to this protocol.

Type of Study:


Study Design:

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

Outcome Measure:

MTD of Naive TCD DLI

Outcome Description:

To determine the maximum tolerated dose (MTD) of a Naive T cell depleted (TCD) donor lymphocyte infusion (DLI) post alemtuzumab-containing allogeneic transplant procedure from a 3-5/6 HLA matched family donor, HLA-identical family donor, or an 8/8 HLA-matched unrelated donor and derive a preliminary assessment of the efficacy of the naive T-cell depleted DLI.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Mitchell Horwitz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

June 2012

Completion Date:

June 2018

Related Keywords:

  • Hematological Malignancies
  • Naive T Cell Depletion
  • Donor Lymphocyte Infusion
  • Allogeneic Hematopoietic Stem Cell Transplant
  • Neoplasms
  • Hematologic Neoplasms



Duke University Medical Center Durham, North Carolina  27710