- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01627275
Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant
February 12, 2018 updated by: Mitchell Horwitz, MD
Naive T-Cell Depleted Donor Lymphocyte Infusion Following Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation 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 and a subset of donor T-cells mediate graft-versus-host disease while other subsets provide the foundation for immune recovery.
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.
The study hypothesis is depletion of naïve T-cells from the donor lymphocyte inoculum will not cause GVHD while providing T-cells to affect both anti-infection and anti-tumor responses.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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 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.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients who have undergone an alemtuzumab or thymoglobulin-containing allogeneic transplant procedure from an 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: DLI from HLA-identical donor
Naive T Cell Depleted Donor Lymphocyte Infusion from HLA matched family member donor or 8/8 HLA matched unrelated donor.
|
A single naive T-cell depleted donor lymphocyte infusion will be administered through a peripheral or central venous catheter greater than or equal to 60 days post allogeneic hematopoietic stem cell transplant.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD of Naive TCD DLI
Time Frame: 12 months
|
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 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.
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunological Recovery
Time Frame: 12 months
|
Immunological recovery will be assessed by the immune function panel which consists of a standardized panel of T-cell, B-cell, NK-cell, and dendritic cell antibodies, measurement of T-cell function, analysis of B-cell recovery, quantification of Naive T-cell recovery and a T-cell repertoire assay.
|
12 months
|
Overall Incidence of Acute GVHD
Time Frame: 60 Days
|
To assess the overall incidence of Acute Graft Versus Host Disease
|
60 Days
|
Overall Incidence of Opportunistic Infections
Time Frame: 60 Days
|
To assess the overall incidence of opportunistic infections
|
60 Days
|
Overall Incidence of Chronic GVHD
Time Frame: 12 months
|
To assess overall incidence of Chronic Graft Versus Host Disease
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2012
Primary Completion (ACTUAL)
February 24, 2017
Study Completion (ACTUAL)
August 3, 2017
Study Registration Dates
First Submitted
June 21, 2012
First Submitted That Met QC Criteria
June 22, 2012
First Posted (ESTIMATE)
June 25, 2012
Study Record Updates
Last Update Posted (ACTUAL)
February 13, 2018
Last Update Submitted That Met QC Criteria
February 12, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00003975
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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