Cytomegalovirus InfectionPhase 1/2VISITNCT02702427
Virus-specific ImmunoTherapy Following Allogeneic Stem Cell Transplantation
A Phase 1/2 study testing virus-specific T-Cells in people with Cytomegalovirus Infection and Adenovirus Infection, run by St. Anna Kinderkrebsforschung at 1 site in Austria.
Trial summary
Invasive infections with CMV and Adenovirus, not responding to virostatic treatment are treated with virusspecific donor derived or autologous virusspecific T-cells. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Cytomegalovirus Infection, Adenovirus Infection
- What is being tested?
- virus-specific T-Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteAustria
- Study dates
- 3 Aug 2016to 1 Apr 2019
- Phase
- Phase 1/2
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age at timepoint of HSCT ≤18 years undergoing allogeneic stem cell transplantation
- Presence of HAdV or CMV-specific T-cells in the donor or CMV-specific T-cells in the recipient pre-transplant
- Stable (≥ 10E6) or increasing viremia despite antiviral treatment post HSCT
- Absence of HAdV or CMV -specific T cells post HSCT
- Karnofsky / Lansky score >50%
- Pregnancy excluded
- Informed study participation consent is signed
Who cannot join
- Infusion of polyclonal or monoclonal T-cell directed antibodies within 28 days before seVirus T-Cell infusion
- Multiple organ failure at screening-timepoint seVirus T-Cell infusion
- History of GvHD Gr III-IV or actual GvHD Gr III-IV
- Pregnancy
- Treatment with granulocyte transfusion within the last 72 hours
- Karnofsky / Lansky score <50%
- Subject is unwilling or unable to comply with the study procedures
- High dose treatment with steroids (≥ 2mg/kg/d, methylprednisone-equivalent)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II: Treatment of Adenovirus and Cytomegalovirus Infection Post Human Allogeneic Stem Cell Transplantation With Short-term Expanded Virus-specific T Cells
Invasive infections with CMV and Adenovirus, not responding to virostatic treatment are treated with virusspecific donor derived or autologous virusspecific T-cells.
Read the detailed description
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment option for several haematological diseases. In spite of substantial progress in this field, viral infections, mainly cytomegalovirus (CMV) and adenovirus (HAdV) in the context of delayed immunoreconstitution remain life threatening complications. Weekly screening of high-risk patients and preemptive virostatic treatment has become a current strategy. Unfortunately, treatment with virostatic drugs is associated with substantial nephro- and myelo-toxicity and of limited effectiveness. Human adenovirus (HAdV) and cytomegalvirus (CMV) disseminated infections are associated with mortality rates of up to 50%-60% despite virostatic treatment.
All HSCT patients at the St. Anna Children's Hospital undergo weekly viral quantitative PCR-screening for HAdV and CMV and weekly PB FACS (Fluorescence Activated Cell Sorter)-Analysis according to the local HSCT-diagnostic SOP (Standard Operating Procedure) from day -7 until day +100 Patients with HAdV or CMV viremia will receive preemptive treatment with either gancyclovir (in case of isolated CMV-viremia) or Cidofovir (in case of HAdV viremia or combined HAdV/CMV infection). In case of increasing viremia ≥ 1log despite antiviral treatment for two weeks or stable with 10E6 viral load and the absence of virus specific T-cells in the recipient, the treating physician will check, if the patient is eligible for seVirus-T-cell infusion (see inclusion criteria).
Study Design: Mononuclear Donor-Cells from peripheral blood (100 ml extra donation) will be cryopreserved at the time-point of HSCT. In case of progredient viremia these cells will be stimulated with interleukin-15 and peptides out of the virus molecule, virusspecific T-Cells are enriched for 2-3 logs-teps and potentially alloreactive cells diluted at the same time. This new approach reduces the risk of graft-versus-host-disease (GvHD) and enables the infusion of virus-specific T-cells also from haploidentical donors.
- Conditions
- Cytomegalovirus Infection, Adenovirus Infection
- Being tested
- virus-specific T-Cells
- Keywords
- viral infections post HSCT, virus-specific T-cells
- Medical subject headings
- Cytomegalovirus Infections, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
virus-specific T-CellsBiological
infusion
| Study group | Role | What they receive |
|---|---|---|
| ARM 1 | Experimental | Patients with Adenovirus or CMV infection after HSCT and no reduction of viral disease or stable disease with 10E6 viral copies within 2 weeks of antiviral treatment will receive a single infusion of virus-specific T-Cells Receives: Biological: virus-specific T-Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non pre-existing Immune System Disorders i.e. Allergic reaction, Anaphylaxis, Cytokine release syndrome or Serum sickness of Grade III-IV of seVirus-T-cell infusion within 48 hours from infusion
assessment is performed according to CTCAE 4.3 Scale
Measured: 48 hours
De novo acute GvHD > Gr II or increase of pre-existing GvHD more than 1 grade from 2 weeks post infusion until 8 weeks post infusion
assessment is performed according to Glucksberg Scale, modified for paediatic patients from D. Jacobsohn (publication Blood 2008)
Measured: 8 weeks
Incidence of graft rejection
Measured: 8 weeks
Secondary outcomes (3)
Detection of virus-specific T-cells within 8 weeks after T-cell therapy. Measurement of the viral load following the infusion of seVirus-T-cells
Measured: 6 months
Correlation of the presence of virus-specific T-cells with partial reduction (>1 log viral copies /ml blood) or complete clearance of viral load
Measured: 8 weeks
Tracking of the infused T-cells by NGS (Next Generation Sequencing) of the TCRs (T-Cell Receptors)-beta rearrangements
PBMCs (isolated from about 10ml of peripheral blood) will be resuspended in TRIzol, a ready to use mixture important for later DNA isolation.
The samples will undergo DNA isolation using a multiplex TCR-beta PCR approach in combination with NGS of the generated amplicons and detailed bioinformatic interpretation of the generated sequence data.
Current high-throughput sequencing technologies such as Illumina, (HiSeq) enable the analysis of T-cell receptor repertoires in an unprecedented depth.
As every T-cell harbours a unique TCR-beta rearrangement, we will be able to track T-cell expansion even on a single cell level.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study start3 Aug 2016
- Primary completion1 Apr 2019
- Study completion1 Apr 2019
Why it stopped: unsuccessful recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Anna Kinderkrebsforschung
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susanne Matthes, MD, Principal investigator, St. Anna Kinderkrebsforschung
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02702427
- Sponsor's protocol ID
- Eudra CT2013-002492-17
- Acronym
- VISIT
- Status last verified
- May 2019
- First submitted
- 1 Mar 2016
- Last updated
- 9 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: not planned yet
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II: Treatment of Adenovirus and Cytomegalovirus Infection Post Human Allogeneic Stem Cell Transplantation With Short-term Expanded Virus-specific T Cells
- ClinicalTrials.gov ID
- NCT02702427
- Acronym / sponsor ID
- VISIT / Eudra CT2013-002492-17
- Conditions
- Cytomegalovirus Infection, Adenovirus Infection
- Keywords
- viral infections post HSCT, virus-specific T-cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: unsuccessful recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- St. Anna KinderkrebsforschungUniversity, hospital or other
- Study start
- 3 Aug 2016 (actual)
- Primary completion
- 1 Apr 2019 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 8 Mar 2016 (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.
Invasive infections with CMV and Adenovirus, not responding to virostatic treatment are treated with virusspecific donor derived or autologous virusspecific T-cells.
Detailed description
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment option for several haematological diseases. In spite of substantial progress in this field, viral infections, mainly cytomegalovirus (CMV) and adenovirus (HAdV) in the context of delayed immunoreconstitution remain life threatening complications. Weekly screening of high-risk patients and preemptive virostatic treatment has become a current strategy. Unfortunately, treatment with virostatic drugs is associated with substantial nephro- and myelo-toxicity and of limited effectiveness. Human adenovirus (HAdV) and cytomegalvirus (CMV) disseminated infections are associated with mortality rates of up to 50%-60% despite virostatic treatment.
All HSCT patients at the St. Anna Children's Hospital undergo weekly viral quantitative PCR-screening for HAdV and CMV and weekly PB FACS (Fluorescence Activated Cell Sorter)-Analysis according to the local HSCT-diagnostic SOP (Standard Operating Procedure) from day -7 until day +100 Patients with HAdV or CMV viremia will receive preemptive treatment with either gancyclovir (in case of isolated CMV-viremia) or Cidofovir (in case of HAdV viremia or combined HAdV/CMV infection). In case of increasing viremia ≥ 1log despite antiviral treatment for two weeks or stable with 10E6 viral load and the absence of virus specific T-cells in the recipient, the treating physician will check, if the patient is eligible for seVirus-T-cell infusion (see inclusion criteria).
Study Design: Mononuclear Donor-Cells from peripheral blood (100 ml extra donation) will be cryopreserved at the time-point of HSCT. In case of progredient viremia these cells will be stimulated with interleukin-15 and peptides out of the virus molecule, virusspecific T-Cells are enriched for 2-3 logs-teps and potentially alloreactive cells diluted at the same time. This new approach reduces the risk of graft-versus-host-disease (GvHD) and enables the infusion of virus-specific T-cells also from haploidentical donors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ARM 1 | Experimental | Biological: virus-specific T-CellsPatients with Adenovirus or CMV infection after HSCT and no reduction of viral disease or stable disease with 10E6 viral copies within 2 weeks of antiviral treatment will receive a single infusion of virus-specific T-Cells |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Age at timepoint of HSCT ≤18 years undergoing allogeneic stem cell transplantation
- Presence of HAdV or CMV-specific T-cells in the donor or CMV-specific T-cells in the recipient pre-transplant
- Stable (≥ 10E6) or increasing viremia despite antiviral treatment post HSCT
- Absence of HAdV or CMV -specific T cells post HSCT
- Karnofsky / Lansky score >50%
Key exclusion criteria (8 listed)
- Infusion of polyclonal or monoclonal T-cell directed antibodies within 28 days before seVirus T-Cell infusion
- Multiple organ failure at screening-timepoint seVirus T-Cell infusion
- History of GvHD Gr III-IV or actual GvHD Gr III-IV
- Pregnancy
- Treatment with granulocyte transfusion within the last 72 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| virus-specific T-Cellsinfusion | Biological | ARM 1 |
Primary outcome
Non pre-existing Immune System Disorders i.e. Allergic reaction, Anaphylaxis, Cytokine release syndrome or Serum sickness of Grade III-IV of seVirus-T-cell infusion within 48 hours from infusion
Time frame: 48 hours
assessment is performed according to CTCAE 4.3 Scale
De novo acute GvHD > Gr II or increase of pre-existing GvHD more than 1 grade from 2 weeks post infusion until 8 weeks post infusion
Time frame: 8 weeks
assessment is performed according to Glucksberg Scale, modified for paediatic patients from D. Jacobsohn (publication Blood 2008)
Incidence of graft rejection
Time frame: 8 weeks
3 secondary outcomes
Detection of virus-specific T-cells within 8 weeks after T-cell therapy. Measurement of the viral load following the infusion of seVirus-T-cells
Time frame: 6 months
Correlation of the presence of virus-specific T-cells with partial reduction (>1 log viral copies /ml blood) or complete clearance of viral load
Time frame: 8 weeks
Tracking of the infused T-cells by NGS (Next Generation Sequencing) of the TCRs (T-Cell Receptors)-beta rearrangements
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2019.
- Individual participant dataSharing planned: No. not planned yet
Related trials for Cytomegalovirus Infection
RecruitingObservational study
The Natural History of Severe Viral Infections and Characterization of Immune Defects in Patients Without Known Immunocompromise
EBV, HSV
RecruitingPhase 1
TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.
Viral Infection
RecruitingPhase 2
CMV CTLs in Neonates With CMV Infection
Congenital Cytomegaloviral (CMV) Disease
RecruitingPhase 2
Virus Specific Cytotoxic T-Lymphocytes (CTLs) for Refractory Cytomegalovirus (CMV)
Cytomegalovirus Infections, Primary Immune Deficiency Disorder
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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.
Susanne Matthes, MD principal investigator
St. Anna Kinderkrebsforschung
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing virus-specific T-Cells in people with Cytomegalovirus Infection and Adenovirus Infection, run by St. Anna Kinderkrebsforschung at 1 site in Austria.
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 7 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: withdrawn, as of the sponsor's last update on 9 May 2019. 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 Austria. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Non pre-existing Immune System Disorders i.e. Allergic reaction, Anaphylaxis, Cytokine release syndrome or Serum sickness of Grade III-IV of seVirus-T-cell infusion within 48 hours from infusion (time frame: 48 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 May 2019.