Clinical Validation of Lophius Biosciences Kit T-Track® CMV in Allo-HSCT Recipients

Cytomegalovirus Infection Clinical Trial

— AlloProtectCMV  

Official title:

Clinical Validation of an Improved T-Track® CMV Assay to Assess the Functionality of CMV Protein-reactive Cell-mediated Immunity (CMI) and Its Suitability to Determine a Protective Cut-off Value for Recurrent CMV Reactivations in Allo-HSCT Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02156479
• Other study ID #: LB-B1
• Status: Completed
• Start date: July 2014
• Est. completion date: April 2018

Study information

• Verified date: August 2018
• Source: Lophius Biosciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study in a cohort of allo-HSCT recipients aims to validate the suitability of an improved T-Track® CMV assay to assess the functionality of CMV protein-reactive effector cells and its suitability to determine cut-off values mediating protection from recurrent CMV reactivations in allo-HSCT recipients.

Lophius T-Track® CMV represents a highly standardized and sensitive diagnostic tool to assess the functionality of a network of clinically relevant CMV-reactive effector cells. It is based on the stimulation of peripheral blood mononuclear cells (PBMC) with activated immunodominant CMV proteins, pp65 and IE-1, and the subsequent quantification of CMV-specific CMI (spot forming colonies) using a highly sensitive IFN-γ ELISpot.

Description:

CMV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with significant morbidity and increased overall mortality. Patients are generally pre-emptively treated with antiviral medication after elevated levels of CMV copies in peripheral blood or plasma have been detected by quantitative PCR. However, these CMV reactivations are often subclinical and do not lead to complications or CMV disease. In these cases functional CMV- specific effector cells have been shown to mediate protection from clinical symptoms. Monitoring of CMV- specific effector cells after allo-HSCT could help to prevent severe side effects due to unnecessary antiviral treatment.

Since the majority of patients develops more than one episode of CMV reactivation, determination of functional CMV-reactive effector cells of cell mediated immunity (CMI) could also help to predict the likelihood of relapsing CMV reactivations and thereby adjust the need for and duration of secondary prophylaxis.

Currently available techniques to measure CMV-specific effector cells lack either a functional read out (multimer stain) or are time consuming and difficult to standardize (detection of intracellular interferon gamma (IFN-ᵞ) after in vitro stimulation using flow cytometry). The improved T-Track® CMV assay has the advantage of combining a standardized and highly sensitive test system with a functional read out (IFN-ᵞ production) considering the function of antigen presenting cells (APC) and different populations of clinically relevant effector cells (CTL, T helper-, NK-, NKT cells). Based on experiences of the performance of this assay system in healthy individuals and hemodialysis patients (the latter as part of a performance evaluation - EUDAMED number 00015561) the presented trial aims to validate an improved variant of this test (including optimized, LPS-depleted IE-1 protein) with regard to its suitability to predict freedom from relapse of CMV-reactivation following treatment of CMV reactivation in a cohort of 120-150 patients after allo-HSCT. Moreover, the results will be compared to (i) analysis of leukocyte subpopulations and (ii) multimer techniques detecting CMV-specific CD8 positive T lymphocytes (CTL) (optional).

Demonstrating the suitability of the improved T-Track® CMV assay to identify patients at reduced risk for recurrent CMV-reactivation, CMV disease or GvHD would highly improve and optimize follow-up care after allo-HSCT regarding therapy success as well as reduced public health care costs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients receiving an allogeneic hematopoietic stem cell transplantation being either CMV seropositive or receiving a graft from a CMV seropositive donor or both, donor and recipient are CMV seropositive (D+/R-, D-/R+, D+/R+)

• Patients receiving a first allogeneic hematopoietic stem cell graft

• Patient at least 18 years of age

• Written informed consent

Exclusion Criteria:

• Seronegativity for CMV both for patient and donor (D-/R-)

• Patients receiving standard anti-CMV prophylaxis

• Patients receiving a haploidentical allogeneic hematopoietic stem cell graft

• Patients receiving an umbilical cord blood graft

• Patients treated with Alemtuzumab (e.g. Campath)

• Patient has any form of substance abuse, psychiatric disorder or condition that, in the opinion of the investigator may invalidate communication with the investigator

• Lack or withdrawal of informed consent

• Patient is unable to comply with the visit schedule in the protocol

Related Conditions & MeSH terms

• Cytomegalovirus Infection
• Cytomegalovirus Infections
• GVHD

Locations

Country	Name	City	State
Germany	Universitätsklinikum Regensburg	Regensburg

Sponsors (2)

Lead Sponsor	Collaborator
Lophius Biosciences GmbH	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Determination of numbers of CMV-specific CTL applying a multimer staining for CMV epitopes		In parallel withT-Track® CMV, thus days 45, 60 and 80 post Tx as well as at any time between day 45 - 225 in case of CMV-complications, optional
Other	Determination of occurrence and severity of GvHD		Any time during study period (day 0 - 225)
Primary	Determination of changes in pp65 and/or IE-1 specific CMI applying T-Track® CMV		days 45, 60 and 80 post Tx as well as at any time between day 45 - 225 in case of CMV-complications
Secondary	Changes in CMV viral load measured by CMV-PCR		As defined in the respective guidelines of the participating institutes, at least in parallel with T-Track® CMV, any time between day 0 - 225
Secondary	Determination of frequencies of leukocyte subpopulations	Numbers of naïve (CD45RA) and memory (CD45RO) CD4 and CD8 positive T cells (CD3) as well as NK cells (CD56) and monocytes (CD14) determined by flow cytometry	In parallel with T-Track® CMV, thus days 45, 60 and 80 post Tx as well as at any time between day 45 - 225 in case of CMV-complications

External Links

•   Lophius Biosciences GmbH