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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02337595
Other study ID # CD45RA_NEG_DLI_2014FRCPHOI
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received January 9, 2015
Last updated January 12, 2015
Start date August 2014
Est. completion date January 2016

Study information

Verified date January 2015
Source Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Contact Michael Maschan, MD
Phone 007 916 651 2145
Email mmaschan@yandex.ru
Is FDA regulated No
Health authority Russian Federation: Ministry of Health
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date January 2016
Est. primary completion date March 2015
Accepts healthy volunteers No
Gender Both
Age group N/A to 25 Years
Eligibility 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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention


Intervention

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

Locations

Country Name City State
Russian Federation Federal Research Center for pediatric hematology, oncology and immunology Moscow

Sponsors (1)

Lead Sponsor Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Country where clinical trial is conducted

Russian Federation, 

References & Publications (1)

Teschner D, Distler E, Wehler D, Frey M, Marandiuc D, Langeveld K, Theobald M, Thomas S, Herr W. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014 Jan;49(1):138-44. doi: 10.1038/bmt.2013.114. Epub 2013 Aug 12. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Cumulative incidence of grade 2-4 acute graft-versus-host disease Cumulative incidence (competing risk model) of acute graft-versus-host disease 100 days Yes
Primary Immune reconstitution (Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay) Quantitative evaluation of lymphocyte subsets in the peripheral blood, quantitative evaluation of pathogen-specific immune response by ELISPOT assay 120 days No
Secondary 1-year survival Kaplan-Meyer estimate of overall survival 1 year No
Secondary Transplant-related mortality Cumulative incidence (competing risk model) of transplant-related mortality 1-year No
Secondary Incidence of chronic graft-versus-host disease Cumulative incidence (competing risk model) of chronic graft-versus-host disease 1 year Yes
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