CD45RA Depleted T-cell Infusion for Prevention of Infections After TCRab/CD19-depleted Allo-HSCT

Lymphoma Clinical Trial

Official title:

A Phase II Prospective Randomized Trial of Donor T-memory Cells (CD45RA Depleted) Infusion for Prevention of Infections After Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02942173
• Other study ID #: CD45RAndom_2016_1
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 2016
• Est. completion date: August 21, 2020

Study information

• Verified date: March 2023
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this prospective randomized study is to determine whether infusions of T-memory cells prevent infections in children with leukemia after allogeneic alpha, beta T-cell receptor (TcRab)/CD19-depleted hematopoietic stem cell transplantation (HSCT).

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 previous pilot protocol the investigators confirmed that infusion after TCR-alpha/beta depleted transplantation of low doses of CD45RA-depleted mononuclear cells are safe and potentially protective against viral infections. The biologic readout for the protocol was a quantitative assessment of T-cell reactivity to common pathogens after infusion and owing to the trial results expansion of CMV-specific CD8 T-cells was discovered in most of the patients. In current randomized protocol the investigators are posing a question if donor lymphocytes infusion (DLI) of low doses of CD45RA-depleted mononuclear cells are effective in viral prophylaxis after TCR-alpha/beta depleted transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: August 21, 2020
• Est. primary completion date: August 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

Inclusion Criteria:

• Patients who are considered candidates for allogeneic hematopoietic stem cell

transplantation and have one of the following diagnoses:

• Acute lymphocytic leukemia (ALL)
• Acute myeloid leukemia
• Acute biphenotypic leukemia
• Acute bilinear leukemia
• Lymphoma
• Myelodysplastic syndrome
• Chronic myeloid leukemia
• Transplant processing: TCR ab/CD19-depletion
• Donors:
• HLA-match unrelated volunteers
• Partly and haploidentical relative

Exclusion Criteria:

• ALL patients not in remission
• Patients with uncontrolled infections
• Clearance of creatinine < 70 ml/min
• Cardiac ejection fraction < 40%
• Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is < 92% on room air
• Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal
• Mental disease of both patient, patient's tutor (if patient is under age 18) and donor, that hinder understanding of main point of the study and keeping treatment plan, hygiene and sanitation

Related Conditions & MeSH terms

• Communicable Diseases
• Graft vs Host Disease
• Graft-versus-Host Disease
• GvHD
• Infections
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Opportunistic Infections

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cumulative incidence of the probability of CMV-reactivation after HSCT		120 days after HSCT
Primary	cumulative incidence of acute GVHD grade II-IV.		150 days after HSCT
Secondary	cumulative incidence of of CMV-disease at 100,180 and 365 days after HSCT		100, 180 and 365 days after HSCT
Secondary	overall survival at 365 days after HSCT		365 days after HSCT
Secondary	Event-free survival at 365 days after HSCT		365 days after HSCT
Secondary	cumulative incidence of relapse at 6 months and 365 days after HSCT		6 months and 365 days
Secondary	cumulative incidence of transplant-related mortality at 6 months after HSCT		6 months
Secondary	cumulative incidence of chronic GvHD		1 year after HSCT
Secondary	cumulative incidence of neutrophil and platelets engraftment at 14 and 30 days after HSCT		14 and 30 days