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

Leukemia, Myeloid, Acute Clinical Trial

— 45RA_NEG_DLI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02337595
• Other study ID #: CD45RA_NEG_DLI_2014FRCPHOI
• 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

Related Conditions & MeSH terms

• Bone Marrow Failure Syndromes
• Deficiency Diseases
• Graft vs Host Disease
• Hemoglobinuria, Paroxysmal
• Immune Deficiency Disease
• Immunologic Deficiency Syndromes
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Opportunistic Infections
• Pancytopenia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

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