Hematological MalignanciesPhase 1NCT01627275
Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant
A Phase 1 study testing Naive T Cell Depleted Donor Lymphocyte Infusion in people with Hematological Malignancies, run by Mitchell Horwitz, MD at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancies
- What is being tested?
- Naive T Cell Depleted Donor Lymphocyte Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to 3 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- Pregnant or lactating women.
- Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: 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.
Read the 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.
- Conditions
- Hematological Malignancies
- Being tested
- Naive T Cell Depleted Donor Lymphocyte Infusion
- Keywords
- Naive T Cell Depletion, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Stem Cell Transplant
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naive T Cell Depleted Donor Lymphocyte InfusionBiological
Also called CD45RA+ T Cells
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.
| Study group | Role | What they receive |
|---|---|---|
| DLI from HLA-identical donor | Experimental | Naive T Cell Depleted Donor Lymphocyte Infusion from HLA matched family member donor or 8/8 HLA matched unrelated donor. Receives: Biological: Naive T Cell Depleted Donor Lymphocyte Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of Naive TCD DLI
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.
Measured: 12 months
Secondary outcomes (4)
Immunological Recovery
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.
Measured: 12 months
Overall Incidence of Acute GVHD
To assess the overall incidence of Acute Graft Versus Host Disease
Measured: 60 Days
Overall Incidence of Opportunistic Infections
To assess the overall incidence of opportunistic infections
Measured: 60 Days
Overall Incidence of Chronic GVHD
To assess overall incidence of Chronic Graft Versus Host Disease
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2012 (estimated)
- Study startJun 2012
- Primary completion24 Feb 2017
- Study completion3 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mitchell Horwitz, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mitchell Horwitz, MD, Duke University
- Investigators
- Mitchell Horwitz, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01627275
- Sponsor's protocol ID
- Pro00003975
- Status last verified
- Feb 2018
- First submitted
- 21 Jun 2012
- Last updated
- 13 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Naive T-Cell Depleted Donor Lymphocyte Infusion Following Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01627275
- Acronym / sponsor ID
- Pro00003975
- Conditions
- Hematological Malignancies
- Keywords
- Naive T Cell Depletion, Donor Lymphocyte Infusion, Allogeneic Hematopoietic Stem Cell Transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Mitchell Horwitz, MDUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- 24 Feb 2017 (actual)
- Study completion
- 3 Aug 2017 (actual)
- First posted
- 25 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DLI from HLA-identical donor | Experimental | Biological: Naive T Cell Depleted Donor Lymphocyte InfusionNaive T Cell Depleted Donor Lymphocyte Infusion from HLA matched family member donor or 8/8 HLA matched unrelated donor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (2 listed)
- Pregnant or lactating women.
- Patients with other major medical or psychiatric illnesses, which the treating physician feels, could seriously compromise tolerance to this protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naive T Cell Depleted Donor Lymphocyte InfusionAlso: CD45RA+ T CellsA 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. | Biological | DLI from HLA-identical donor |
Primary outcome
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.
4 secondary outcomes
Immunological Recovery
Time frame: 12 months
Overall Incidence of Acute GVHD
Time frame: 60 Days
Overall Incidence of Opportunistic Infections
Time frame: 60 Days
Overall Incidence of Chronic GVHD
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchell Horwitz, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Naive T Cell Depleted Donor Lymphocyte Infusion in people with Hematological Malignancies, run by Mitchell Horwitz, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD of Naive TCD DLI (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2018.