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

April 21, 2016 updated by: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Transfusion of CD45RA-depleted Donor Lymphocytes to Improve Regeneration of Antimicrobial 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 117997
        • Federal Research Center for pediatric hematology, oncology and immunology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
100 days
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
120 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1-year survival
Time Frame: 1 year
Kaplan-Meyer estimate of overall survival
1 year
Transplant-related mortality
Time Frame: 1-year
Cumulative incidence (competing risk model) of transplant-related mortality
1-year
Incidence of chronic graft-versus-host disease
Time Frame: 1 year
Cumulative incidence (competing risk model) of chronic graft-versus-host disease
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Investigators

  • Principal Investigator: Michael Maschan, MD, Fedaral Research Center for pediatric hematology, oncology and immunology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2014

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

January 9, 2015

First Submitted That Met QC Criteria

January 12, 2015

First Posted (Estimate)

January 13, 2015

Study Record Updates

Last Update Posted (Estimate)

April 22, 2016

Last Update Submitted That Met QC Criteria

April 21, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CD45RA_NEG_DLI_2014FRCPHOI

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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