Precursor T-Cell Lymphoblastic Leukemia-LymphomaPhase 1/245RA_NEG_DLINCT02337595
Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
A Phase 1/2 study testing CD45RA-depleted peripheral blood mononuclear cells in people with Precursor T-Cell Lymphoblastic Leukemia-Lymphoma and Leukemia, Myeloid, Acute, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
The stud will evaluate whether infusions of CD45RA-depleted lymphocytes from the donor early post-transplant is a safe way to improve immunity to common infections in recipients of TCR-alpha/beta depleted hematopoietic stem cell grafts. Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Immune Deficiency Disease
- What is being tested?
- CD45RA-depleted peripheral blood mononuclear cells
- Type of treatment
- Injection or infusion
- How many people
- 30 participants
- Where
- 1 siteRussia
- Study dates
- Aug 2014to Jan 2016
- Phase
- Phase 1/2
- 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 Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- recipient of allogeneic hematopoietic stem cell graft from haploidentical or matched unrelated donor
- TCR alpha/beta depletion of the hematopoietic stem cell graft
- CMV-seropositive donor
- stable hematopoietic engraftment
Who cannot join
- active graft-versus-host disease grade 2-4
- any systemic immune suppressive therapy except calcineurin inhibitor monotherapy
- uncontrolled sepsis
Trial locations and contacts
1 site in 1 country.
Russia1 site
Federal Research Center for pediatric hematology, oncology and immunology
Moscow, 117997
About this study
Official title: Transfusion of CD45RA-depleted Donor Lymphocytes to Improve Regeneration of Antimicrobial Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
The stud will evaluate whether infusions of CD45RA-depleted lymphocytes from the donor early post-transplant is a safe way to improve immunity to common infections in recipients of TCR-alpha/beta depleted hematopoietic stem cell grafts.
Read the detailed description
Graft-versus-host disease (GVHD) remains the most important direct complication of hematopoietic stem cell transplantation. Methods used to prevent GVHD include diverse pharmacologic interventions and ex vivo methods of T-cell depletion, the latter being the most effective ones. Historically depletion of T-cells from the graft is associated with increased rate of graft failure, relapse of malignant disease and prolonged immune deficiency. Selective depletion of TCR-alpha/beta T-lymphocytes is a new method of hematopoietic stem cell graft manipulation which is thought to conserve important cell populations, e.g. NK cells and gamma/delta T cells within the graft. Preliminary results suggest that TCR alpha/beta depletion ensures high engraftment rate, low early mortality and good control of GVHD. The problem of delayed immune reconstitution and life-threatening viral infections remains incompletely resolved.
Depletion of naive (CD45RA-positive) T-cells was developed as a new method of graft manipulation to prevent GVHD. Research data indicate that alloreactivity is associated mainly with naive T-cell fraction. In vitro depletion of CD45RA lowers significantly the alloreactive response while retaining reactivity to pathogens.
In the current protocol we plan to test whether relatively low doses of CD45RA-depleted mononuclear cells can be safely infused after TCR-alpha/beta depleted transplantation. The biologic readout for the protocol will be quantitative assessment of T-cell reactivity to common pathogens after infusion.
- Conditions
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Immune Deficiency Disease, Bone Marrow Failure Syndromes, Opportunistic Infections, Graft vs Host Disease
- Being tested
- CD45RA-depleted peripheral blood mononuclear cells
- Keywords
- CD45RA-depletion, TCR-alpha/beta depletion, Hematopoietic Stem Cell Transplantation, immune reconstitution, Graft Enhancement, Immunologic, Immunocompromized Host
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Immune Deficiency Disease, Bone Marrow Failure Disorders, Opportunistic Infections, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD45RA-depleted peripheral blood mononuclear cellsBiological
Infusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of grade 2-4 acute graft-versus-host disease
Cumulative incidence (competing risk model) of acute graft-versus-host disease
Measured: 100 days
Immune reconstitution (Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay)
Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay
Measured: 120 days
Secondary outcomes (3)
1-year survival
Kaplan-Meyer estimate of overall survival
Measured: 1 year
Transplant-related mortality
Cumulative incidence (competing risk model) of transplant-related mortality
Measured: 1-year
Incidence of chronic graft-versus-host disease
Cumulative incidence (competing risk model) of chronic graft-versus-host disease
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2015 (estimated)
- Study startAug 2014
- Primary completionMar 2015
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Precursor T-Cell Lymphoblastic Leukemia-LymphomaStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Maschan, MD, Principal investigator, Fedaral Research Center for pediatric hematology, oncology and immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02337595
- Sponsor's protocol ID
- CD45RA_NEG_DLI_2014FRCPHOI
- Acronym
- 45RA_NEG_DLI
- Status last verified
- Apr 2016
- First submitted
- 9 Jan 2015
- Last updated
- 22 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014 Jan;49(1):138-44. doi: 10.1038/bmt.2013.114. Epub 2013 Aug 12.
PubMed 23933765Bleakley M, Heimfeld S, Jones LA, Turtle C, Krause D, Riddell SR, Shlomchik W. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol Blood Marrow Transplant. 2014 May;20(5):705-16. doi: 10.1016/j.bbmt.2014.01.032. Epub 2014 Feb 11.
PubMed 24525279
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transfusion of CD45RA-depleted Donor Lymphocytes to Improve Regeneration of Antimicrobial Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT02337595
- Acronym / sponsor ID
- 45RA_NEG_DLI / CD45RA_NEG_DLI_2014FRCPHOI
- Conditions
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Immune Deficiency Disease, Bone Marrow Failure Syndromes, Opportunistic Infections, Graft vs Host Disease
- Keywords
- CD45RA-depletion, TCR-alpha/beta depletion, Hematopoietic Stem Cell Transplantation, immune reconstitution, Graft Enhancement, Immunologic, Immunocompromized Host
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Mar 2015 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 13 Jan 2015 (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.
The stud will evaluate whether infusions of CD45RA-depleted lymphocytes from the donor early post-transplant is a safe way to improve immunity to common infections in recipients of TCR-alpha/beta depleted hematopoietic stem cell grafts.
Detailed description
Graft-versus-host disease (GVHD) remains the most important direct complication of hematopoietic stem cell transplantation. Methods used to prevent GVHD include diverse pharmacologic interventions and ex vivo methods of T-cell depletion, the latter being the most effective ones. Historically depletion of T-cells from the graft is associated with increased rate of graft failure, relapse of malignant disease and prolonged immune deficiency. Selective depletion of TCR-alpha/beta T-lymphocytes is a new method of hematopoietic stem cell graft manipulation which is thought to conserve important cell populations, e.g. NK cells and gamma/delta T cells within the graft. Preliminary results suggest that TCR alpha/beta depletion ensures high engraftment rate, low early mortality and good control of GVHD. The problem of delayed immune reconstitution and life-threatening viral infections remains incompletely resolved.
Depletion of naive (CD45RA-positive) T-cells was developed as a new method of graft manipulation to prevent GVHD. Research data indicate that alloreactivity is associated mainly with naive T-cell fraction. In vitro depletion of CD45RA lowers significantly the alloreactive response while retaining reactivity to pathogens.
In the current protocol we plan to test whether relatively low doses of CD45RA-depleted mononuclear cells can be safely infused after TCR-alpha/beta depleted transplantation. The biologic readout for the protocol will be quantitative assessment of T-cell reactivity to common pathogens after infusion.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- recipient of allogeneic hematopoietic stem cell graft from haploidentical or matched unrelated donor
- TCR alpha/beta depletion of the hematopoietic stem cell graft
- CMV-seropositive donor
- stable hematopoietic engraftment
Key exclusion criteria (3 listed)
- active graft-versus-host disease grade 2-4
- any systemic immune suppressive therapy except calcineurin inhibitor monotherapy
- uncontrolled sepsis
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 |
|---|---|---|
| CD45RA-depleted peripheral blood mononuclear cellsInfusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells | Biological | – |
Primary outcome
Cumulative incidence of grade 2-4 acute graft-versus-host disease
Time frame: 100 days
Cumulative incidence (competing risk model) of acute graft-versus-host disease
Immune reconstitution (Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay)
Time frame: 120 days
Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay
3 secondary outcomes
1-year survival
Time frame: 1 year
Transplant-related mortality
Time frame: 1-year
Incidence of chronic graft-versus-host disease
Time frame: 1 year
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 22 Apr 2016.
- Background: PubMed 23933765Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014 Jan;49(1):138-44. doi: 10.1038/bmt.2013.114. Epub 2013 Aug 12.
- Background: PubMed 24525279Bleakley M, Heimfeld S, Jones LA, Turtle C, Krause D, Riddell SR, Shlomchik W. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol Blood Marrow Transplant. 2014 May;20(5):705-16. doi: 10.1016/j.bbmt.2014.01.032. Epub 2014 Feb 11.
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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.
Michael Maschan, MD principal investigator
Fedaral Research Center for pediatric hematology, oncology and immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CD45RA-depleted peripheral blood mononuclear cells in people with Precursor T-Cell Lymphoblastic Leukemia-Lymphoma and Leukemia, Myeloid, Acute, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
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 4 inclusion and 3 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 22 Apr 2016. 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 Russia. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Cumulative incidence of grade 2-4 acute graft-versus-host disease (time frame: 100 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02337595, which also lists 2 linked publications.
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 22 Apr 2016.