Cytomegalovirus InfectionAlloProtectCMVNCT02156479
Clinical Validation of Lophius Biosciences Kit T-Track® CMV in Allo-HSCT Recipients
An observational study of Cytomegalovirus Infection and GVHD, run by Lophius Biosciences GmbH at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infection, GVHD
- How many people
- 175 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2014to Apr 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients receiving an allogeneic hematopoietic stem cell transplantation for the first time, being either CMV seropositive or receiving a graft from a CMV seropositive donor or both, donor and recipient are CMV seropositive
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed 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.
- Conditions
- Cytomegalovirus Infection, GVHD
- Keywords
- CMV, T-Track CMV, allo-HSCT, CMI
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Allo-HSCT recipients | Patients receiving an allogeneic hematopoietic stem cell transplantation for the first time, being either CMV seropositive or receiving a graft from a CMV seropositive donor or both, donor and recipient are CMV seropositive |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of changes in pp65 and/or IE-1 specific CMI applying T-Track® CMV
Measured: days 45, 60 and 80 post Tx as well as at any time between day 45 - 225 in case of CMV-complications
Secondary outcomes (2)
Changes in CMV viral load measured by CMV-PCR
Measured: As defined in the respective guidelines of the participating institutes, at least in parallel with T-Track® CMV, any time between day 0 - 225
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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2014 (estimated)
- Study startJul 2014
- Primary completionApr 2018
- Study completionApr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytomegalovirus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lophius Biosciences GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- German Federal Ministry of Education and Research
- Responsible party
- Sponsor
- Investigators
- Daniel Wolff, Prof. Dr. med., Principal investigator, Klinik für Innere Medizin III, Hämatologie und Onkologie Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02156479
- Sponsor's protocol ID
- LB-B1
- Acronym
- AlloProtectCMV
- Status last verified
- Aug 2018
- First submitted
- 27 May 2014
- Last updated
- 8 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Wagner-Drouet E, Teschner D, Wolschke C, Janson D, Schafer-Eckart K, Gartner J, Mielke S, Schreder M, Kobbe G, Kondakci M, Hilgendorf I, von Lilienfeld-Toal M, Klein S, Heidenreich D, Kreil S, Verbeek M, Grass S, Ditschkowski M, Gromke T, Koch M, Lindemann M, Hunig T, Schmidt T, Rascle A, Guldan H, Barabas S, Deml L, Wagner R, Wolff D. Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. Haematologica. 2021 Feb 1;106(2):363-374. doi: 10.3324/haematol.2019.229252.
PubMed 31879324
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02156479
- Acronym / sponsor ID
- AlloProtectCMV / LB-B1
- Conditions
- Cytomegalovirus Infection, GVHD
- Keywords
- CMV, T-Track CMV, allo-HSCT, CMI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- Lophius Biosciences GmbHIndustry (pharma, biotech, devices)
- Collaborators
- German Federal Ministry of Education and Research
- Study start
- Jul 2014 (actual)
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 5 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allo-HSCT recipients | – | –Patients receiving an allogeneic hematopoietic stem cell transplantation for the first time, being either CMV seropositive or receiving a graft from a CMV seropositive donor or both, donor and recipient are CMV seropositive |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients receiving an allogeneic hematopoietic stem cell transplantation for the first time, being either CMV seropositive or receiving a graft from a CMV seropositive donor or both, donor and recipient are CMV seropositive
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Determination of changes in pp65 and/or IE-1 specific CMI applying T-Track® CMV
Time frame: days 45, 60 and 80 post Tx as well as at any time between day 45 - 225 in case of CMV-complications
2 secondary outcomes
Changes in CMV viral load measured by CMV-PCR
Time frame: As defined in the respective guidelines of the participating institutes, at least in parallel with T-Track® CMV, any time between day 0 - 225
Determination of frequencies of leukocyte subpopulations
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2018.
- Derived from this study: PubMed 31879324Wagner-Drouet E, Teschner D, Wolschke C, Janson D, Schafer-Eckart K, Gartner J, Mielke S, Schreder M, Kobbe G, Kondakci M, Hilgendorf I, von Lilienfeld-Toal M, Klein S, Heidenreich D, Kreil S, Verbeek M, Grass S, Ditschkowski M, Gromke T, Koch M, Lindemann M, Hunig T, Schmidt T, Rascle A, Guldan H, Barabas S, Deml L, Wagner R, Wolff D. Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. Haematologica. 2021 Feb 1;106(2):363-374. doi: 10.3324/haematol.2019.229252.
- Lophius Biosciences GmbHLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Wolff, Prof. Dr. med. principal investigator
Klinik für Innere Medizin III, Hämatologie und Onkologie Regensburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Infection and GVHD, run by Lophius Biosciences GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of changes in pp65 and/or IE-1 specific CMI applying T-Track® CMV (time frame: days 45, 60 and 80 post Tx as well as at any time between day 45 - 225 in case of CMV-complications). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02156479, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2018.