Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation (45RA_NEG_DLI)
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|ClinicalTrials.gov Identifier: NCT02337595|
Recruitment Status : Completed
First Posted : January 13, 2015
Last Update Posted : April 22, 2016
|Condition or disease||Intervention/treatment||Phase|
|Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Immune Deficiency Disease Bone Marrow Failure Syndromes Opportunistic Infections Graft vs Host Disease||Biological: CD45RA-depleted peripheral blood mononuclear cells||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Transfusion of CD45RA-depleted Donor Lymphocytes to Improve Regeneration of Antimicrobial Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation|
|Study Start Date :||August 2014|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||January 2016|
- Biological: CD45RA-depleted peripheral blood mononuclear cells
Infusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells
- 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
- 1-year survival [ Time Frame: 1 year ]Kaplan-Meyer estimate of overall survival
- Transplant-related mortality [ Time Frame: 1-year ]Cumulative incidence (competing risk model) of transplant-related mortality
- Incidence of chronic graft-versus-host disease [ Time Frame: 1 year ]Cumulative incidence (competing risk model) of chronic graft-versus-host disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337595
|Federal Research Center for pediatric hematology, oncology and immunology|
|Moscow, Russian Federation, 117997|
|Principal Investigator:||Michael Maschan, MD||Fedaral Research Center for pediatric hematology, oncology and immunology|