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

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ClinicalTrials.gov Identifier: NCT02337595
Recruitment Status : Completed
First Posted : January 13, 2015
Last Update Posted : April 22, 2016
Sponsor:
Information provided by (Responsible Party):
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
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 : August 2014
Actual Primary Completion Date : March 2015
Actual Study Completion Date : January 2016



Intervention Details:
  • Biological: CD45RA-depleted peripheral blood mononuclear cells
    Infusion of escalating doses of CD45RA-depleted donor-derived allogeneic peripheral blood mononuclear cells


Primary Outcome Measures :
  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 Outcome Measures :
  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



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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02337595


Locations
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Russian Federation
Federal Research Center for pediatric hematology, oncology and immunology
Moscow, Russian Federation, 117997
Sponsors and Collaborators
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Investigators
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Principal Investigator: Michael Maschan, MD Fedaral Research Center for pediatric hematology, oncology and immunology

Publications:
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Responsible Party: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
ClinicalTrials.gov Identifier: NCT02337595     History of Changes
Other Study ID Numbers: CD45RA_NEG_DLI_2014FRCPHOI
First Posted: January 13, 2015    Key Record Dates
Last Update Posted: April 22, 2016
Last Verified: April 2016

Keywords provided by Federal Research Institute of Pediatric Hematology, Oncology and Immunology:
CD45RA-depletion
TCR-alpha/beta depletion
Hematopoietic Stem Cell Transplantation
immune reconstitution
Graft Enhancement, Immunologic
Immunocompromized Host

Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Immunologic Deficiency Syndromes
Leukemia, Myeloid
Graft vs Host Disease
Opportunistic Infections
Leukemia, Myeloid, Acute
Pancytopenia
Anemia, Aplastic
Hemoglobinuria, Paroxysmal
Deficiency Diseases
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Infection
Virus Diseases
Parasitic Diseases
Hematologic Diseases
Anemia
Bone Marrow Diseases
Anemia, Hemolytic
Myelodysplastic Syndromes
Malnutrition
Nutrition Disorders