45RA_NEG_DLI: Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology (Other)

Overall Status

Completed

CT.gov ID

NCT02337595

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

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

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

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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 :

Aug 1, 2014

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Jan 1, 2016

Outcome Measures

Primary Outcome Measures

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

1-year survival [1 year]
Kaplan-Meyer estimate of overall survival
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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