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

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Biological: CD45RA-depleted peripheral blood mononuclear cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02337595

CD45RA_NEG_DLI_2014FRCPHOI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: Under 25 years old

Volunteers: No 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

Exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)