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Completed

NCT Number: NCT02337595

Memory T-cell Infusion to Improve 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.

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Key information

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Bone Marrow Diseases Bone Marrow Failure Disorders Bone Marrow Failure Syndromes Graft vs Host Disease Hematologic Diseases Hemic and Lymphatic Diseases Immune Deficiency Disease Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myeloid, Acute Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Opportunistic Infections Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

Up to 25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Federal Research Center for pediatric hematology, oncology and immunology

Moscow, 117997, Russia

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

CD45RA-depleted peripheral blood mononuclear cells

Biological

Infusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 1-year survival

    Time frame: 1 year

    Kaplan-Meyer estimate of overall survival

  2. Transplant-related mortality

    Time frame: 1-year

    Cumulative incidence (competing risk model) of transplant-related mortality

  3. Incidence of chronic graft-versus-host disease

    Time frame: 1 year

    Cumulative incidence (competing risk model) of chronic graft-versus-host disease

Sponsors and collaborators

Lead sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Other

Registry information

Official study title

Transfusion of CD45RA-depleted Donor Lymphocytes to Improve Regeneration of Antimicrobial Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation

Acronym: 45RA_NEG_DLI

Important dates

Study start
2014
Primary completion
2015
Study completion
2016
First posted
Jan 13, 2015
Registry last updated
Apr 22, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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