Trial document




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  DRKS00007113

Trial Description

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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

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Trial Acronym

AlloProtect CMV, LB-B1

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URL of the Trial

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Brief Summary in Lay Language

About 50 % of the population in industrialized countries is infected with the human Cytomegalovirus (CMV). In healthy individuals, replication of the virus is tightly controlled by the cytomegalovirus-specific cellular immunity.
However, in allogeneic stem cell transplant patients the immune system has been destroyed due to a strong chemotherapy. The lack of CMV-specific cellular immunity can lead to uncontrolled replication of the virus and associated severe complications until the immune system is restored.
This study aims to investigate whether measurement of Cytomegalovirus-specific cellular immunity using the novel T-Track® CMV assay allows the prognosis and risk assessment of uncontrolled virus-replication and associated severe complications in patients after allogeneic stem cell transplantation.

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Brief Summary in Scientific Language

CMV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains to be 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.

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Organizational Data

  •   DRKS00007113
  •   2015/01/12
  •   2014/05/27
  •   no
  •   Approved
  •   13-122-0282 , Ethikkommission an der Universität Regensburg
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Secondary IDs

  •   NCT02156479   (ClinicalTrials.gov)
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Health Condition or Problem studied

  •   B25.9 -  Cytomegaloviral disease, unspecified
  •   Z94.80 -  [generalization Z94.8: Other transplanted organ and tissue status]
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Interventions/Observational Groups

  •   120-150 patients after allogeneic stem cell transplantation undergoing preemptive antiviral treatment are enrolled in the study. During routine visits at day 45, 60 and 80 after transplantation 18 ml of whole blood are taken to determine CMV-specific CMI using T-Track® CMV assay and the frequencies of leukocyte subpopulations by flow cytometry. The withdrawal of further 9 ml of whole blood for detection of CMV-specific cytotoxic T cells using MHC-Multimers is optional.
    Additional CMV-specific CMI (T-Track® CMV and MHC-Multimers) and leukocyte subpopulation determinations are performed at any day of CMV- reactivation diagnosis or at the next possible visit with routine blood withdrawal (until d10 after CMV reactivation diagnosis) as well as on days 0, 7, 14 after withdrawal of antiviral therapy.
    CMV PCR is performed as defined in the respective guidelines of the participating institutes but at least in parallel with T-Track® CMV. The individual observational period lasts 6 months.
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Characteristics

  •   Non-interventional
  •   Other
  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Prognosis
  •   Single (group)
  •   N/A
  •   N/A
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Primary Outcome

Validation whether screening of CMV-reactive effector cells applying improved T-Track® CMV can predict freedom from relapse of treatment-requiring CMV reactivation following successful antiviral treatment of primary CMV reactivation after allo-HSCT in CMV-seropositive recipients and recipients receiving allografts from CMV-seropositive donors (D+/R+, D+/R-, D-/R+).

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Secondary Outcome

I. Validation whether screening for CMV protein-reactive effector cells applying improved T-Track® CMV can identify patients at reduced risk for primary CMV reactivation requiring antiviral medication.
II. Comparison of the suitability of the numbers of pp65 and/or IE-1- specific effector cells applying improved T-Track® CMV and the frequencies of leukocyte subpopulations for the identification of transplant recipients at reduced risk for primary and recurrent CMV reactivation.
III. Validation whether the numbers of pp65 and/or IE-1 specific effector cells applying T-Track® CMV correlate with the occurrence and severity of GvHD.
IV. Comparison of the suitability of the numbers of pp65 and/or IE-1-specific effector cells applying improved T-Track® CMV and the numbers of CMV-specific CTL applying a multimer staining for CMV epitopes for the identification of transplant recipients at reduced risk for primary and recurrent CMV reactivations.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2014/07/03
  •   150
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

I. 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+)

according to amendment Oct 2015:
Patients receiving an allogeneic hematopoietic stem cell transplantation being CMV seropositive and receiving a graft from a CMV seronegative donor (D-/R+)
II. Patients receiving a first allogeneic hematopoietic stem cell graft
III. Patient at least 18 years of age
IV. Written informed consent

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Exclusion Criteria

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

according to amendment oct 2015: Seronegativity for CMV both for patient and donor (D-/R-) or seropositivity of donor (D+/R-, D+/R+9)
• 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

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Addresses

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    • Lophius Biosciences GmbH
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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    • Lophius Biosciences GmbH
    • Mr.  PD Dr.  Ludwig  Deml 
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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    • Lophius Biosciences GmbH
    • Ms.  Dr.  Traudel  Schmidt 
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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Sources of Monetary or Material Support

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    • Lophius Biosciences GmbH
    • Am BioPark 13
    • 93053  Regensburg
    • Germany
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    • Bundesministerium für Bildung und Forschung Dienstsitz Berlin
    • Friedrichstraße 130 B
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2018/04/12
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.