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

Brief Title

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

Official Title

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

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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Cumulative incidence of grade 2-4 acute graft-versus-host disease

Secondary Outcome

 1-year survival

Condition

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Intervention

CD45RA-depleted peripheral blood mononuclear cells


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

30

Start Date

August 2014

Completion Date

January 2016

Primary Completion Date

March 2015

Eligibility Criteria

        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
      

Gender

All

Ages

N/A - 25 Years

Accepts Healthy Volunteers

No

Contacts

Michael Maschan, MD, , 

Location Countries

Russian Federation

Location Countries

Russian Federation

Administrative Informations


NCT ID

NCT02337595

Organization ID

CD45RA_NEG_DLI_2014FRCPHOI


Responsible Party

Sponsor

Study Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology


Study Sponsor

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


Verification Date

April 2016