Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation

Phase 1

Completed

• Conditions: Opportunistic Infections; Graft vs Host Disease; Immune Deficiency Disease; Bone Marrow Failure Syndromes; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

• Registration Number: NCT02337595
• Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Brief 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.

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 Timeline

• Study Start: 2014-08
• Study First Submitted: 2015-01-09
• Study First Submitted QC: 2015-01-12
• Study First Posted: 2015-01-13
• Primary Completion: 2015-03
• Study Completion: 2016-01
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-21
• Last Update Posted: 2016-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 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

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Exclusion Criteria

• active graft-versus-host disease grade 2-4
• any systemic immune suppressive therapy except calcineurin inhibitor monotherapy
• uncontrolled sepsis

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Cumulative incidence of grade 2-4 acute graft-versus-host disease	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)	120 days	Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay

Secondary Outcome Measures

Name	Time	Method
Transplant-related mortality	1-year	Cumulative incidence (competing risk model) of transplant-related mortality
Incidence of chronic graft-versus-host disease	1 year	Cumulative incidence (competing risk model) of chronic graft-versus-host disease
1-year survival	1 year	Kaplan-Meyer estimate of overall survival

Trial Locations

Locations (1)

Federal Research Center for pediatric hematology, oncology and immunology; 🇷🇺 Moscow, Russian Federation