CMV InfectionPhase 1R3ACTNCT02779439
Partially HLA-matched Third Party Antigen Specific T-cells for Infection Post-stem Cell or Solid Organ Transplantation
A Phase 1 study testing Virus specific CTLs in people with CMV Infection and EBV, run by University of Sydney at 1 site in Australia.
Trial summary
To assess the safety and biological efficacy of therapeutically administered most closely HLA-matched third party donor-derived specific cytotoxic T lymphocytes (CTLs) targeting cytomegalovirus (CMV) or Adenovirus (Adv) or Epstein Barr virus (EBV) or fungi including Aspergillus and Candida species for the treatment of… Read more about this study
- Who is it for?
- Ages 1 year to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- CMV Infection, EBV, Adenovirus
- What is being tested?
- Virus specific CTLs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteAustralia
- Study dates
- Jan 2013to Mar 2018
- Phase
- Phase 1
- 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 1 year to 70 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Recipients of myeloablative or non-myeloablative allogeneic or solid organ transplantation for any indication.
- Presence of viral reactivation or infection with CMV, Adv or EBV or invasive fungal disease must be present at the time of infusion as determined by:
- For CMV CMV detectable by antigen detection, PCR or culture in peripheral blood or tissue biopsy or by immunohistochemical staining on tissue biopsy specimen
- For Adv Presence of Adv as detected by PCR, antigen detection or culture in body fluids including blood, stool, urine or nasopharyngeal secretions
- For EBV Elevated EB virus detectable in peripheral blood by PCR or Presence of documented EBV related PTLD diagnosed by tissue biopsy or Elevated EB virus detectable in the blood by PCR and clinical or imaging findings consistent with EBV lymphoma
- For invasive fungal disease Proven or probable invasive fungal disease according to De Pauw 2008[114]
Show all 18Show fewer
- Failure of standard therapy as defined by:
- For CMV The continued presence of detectable CMV virus or antigen after at least 14 days of antiviral therapy with IV ganciclovir or foscarnet Recurrence of detectable CMV virus or antigen after at least 2 weeks of prior antiviral therapy
- For Adv A rise or less than 50% reduction in viral load in blood or any site of disease as measured by PCR or any quantitative assay despite use of therapy as determined by the treating physician; Standard therapy may include intravenous cidofovir within the limits of renal function
- For EBV Increase or less than 50% decrease in the size of EBV lymphoma or
- Increase or less than 50% decrease in the EBV viral load in peripheral blood despite use of appropriate therapy as determined by the treating physician which may include:
- Reduction in immunosuppression
- Rituximab 375mg/m2 up to 4 infusions
- Cytotoxic chemotherapy
- o For invasive fungal disease inadequate or incomplete clinical response according to treating physician after at least 5 days of best available therapy
- Adequate hepatic and renal function (< 3 x upper limit of normal for AST (SGOT), ALT (SGPT), < 2 x upper limit of normal for total bilirubin, serum creatinine)
- ECOG status 0 to 3 or Lansky score 30-100
- Patient (or legal representative) has given informed consent
Who cannot join
- Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion.
- Grade II or greater graft versus host disease within 1 week prior to infusion.
- Prednisone or methylprednisolone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
- ECOG status 4 or Lansky score <30
- Privately insured in or outpatients in New South Wales participating centres (see 12.5 Indemnity issues).
Trial locations and contacts
1 site in 1 country.
David Gottlieb, MD FRACP contact
Australia1 site, 1 recruiting
- Recruiting
Westmead Hospital
Sydney, New South Wales, 2145
David Gottlieb, MD FRACP, david.gottlieb@sydney.edu.au
About this study
Official title: Therapeutic Infusion of Partially HLA-matched Third Party Donor-derived Virus- and Fungus Specific T-lymphocytes in Patients With Active Viral or Fungal Infection Post-allogeneic Stem Cell or Solid Organ Transplantation
To assess the safety and biological efficacy of therapeutically administered most closely HLA-matched third party donor-derived specific cytotoxic T lymphocytes (CTLs) targeting cytomegalovirus (CMV) or Adenovirus (Adv) or Epstein Barr virus (EBV) or fungi including Aspergillus and Candida species for the treatment of viral infection following allogeneic blood or marrow stem cell or solid organ transplantation.
Read the detailed description
The study will analyse the safety and biological efficacy of administering the investigational products (most closely HLA-matched third party donor-derived T cells stimulated with viral or fungal antigen expressing DC), for the treatment of viral reactivation and/or infection or fungal infection following allogeneic blood or marrow or solid organ transplantation. The cells will be given therapeutically after transplantation in patients with active viral reactivation or proven/probably fungal infection despite standard therapy.
Our AIMS are to study the safety of third party donor-derived CTL infusions, their effect on treatment of viral reactivation as well as their effect on reconstitution of virus- and fungus-specific immunity, viral and fungal infection and reactivation rates after transplantation, viral load, and use of antiviral and antifungal pharmacotherapy.
We will evaluate the safety of infusions with respect to the development of adverse events within the first 12 months post-CTL infusion and the dynamics of cell persistence by T-cell chimerism analysis.
- Conditions
- CMV Infection, EBV, Adenovirus
- Being tested
- Virus specific CTLs
- 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 CTLsBiological
Also called T cells
Virus specific CTLs will be given to patients with persistent or recurrent viral reactivation after 2 weeks of standard anti-viral therapy
| Study group | Role | What they receive |
|---|---|---|
| 3rd party CTL infusion | Experimental | Virus specific CTLs Receives: Biological: Virus specific CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infusion related safety
infusion related adverse events
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2016 (estimated)
- Study startJan 2013
- Primary completionDec 2017 (estimated)
- Study completionMar 2018 (estimated)
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 CMV 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sydney
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Gottlieb, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02779439
- Sponsor's protocol ID
- R3ACT
- Acronym
- R3ACT
- Status last verified
- Jul 2016
- First submitted
- 18 May 2016
- Last updated
- 21 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Withers B, Blyth E, Clancy LE, Yong A, Fraser C, Burgess J, Simms R, Brown R, Kliman D, Dubosq MC, Bishop D, Sutrave G, Ma CKK, Shaw PJ, Micklethwaite KP, Gottlieb DJ. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. Blood Adv. 2017 Nov 2;1(24):2193-2205. doi: 10.1182/bloodadvances.2017010223. eCollection 2017 Nov 14.
PubMed 29296867
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Infusion of Partially HLA-matched Third Party Donor-derived Virus- and Fungus Specific T-lymphocytes in Patients With Active Viral or Fungal Infection Post-allogeneic Stem Cell or Solid Organ Transplantation
- ClinicalTrials.gov ID
- NCT02779439
- Acronym / sponsor ID
- R3ACT / R3ACT
- Conditions
- CMV Infection, EBV, Adenovirus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of SydneyUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 20 May 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.
To assess the safety and biological efficacy of therapeutically administered most closely HLA-matched third party donor-derived specific cytotoxic T lymphocytes (CTLs) targeting cytomegalovirus (CMV) or Adenovirus (Adv) or Epstein Barr virus (EBV) or fungi including Aspergillus and Candida species for the treatment of viral infection following allogeneic blood or marrow stem cell or solid organ transplantation.
Detailed description
The study will analyse the safety and biological efficacy of administering the investigational products (most closely HLA-matched third party donor-derived T cells stimulated with viral or fungal antigen expressing DC), for the treatment of viral reactivation and/or infection or fungal infection following allogeneic blood or marrow or solid organ transplantation. The cells will be given therapeutically after transplantation in patients with active viral reactivation or proven/probably fungal infection despite standard therapy.
Our AIMS are to study the safety of third party donor-derived CTL infusions, their effect on treatment of viral reactivation as well as their effect on reconstitution of virus- and fungus-specific immunity, viral and fungal infection and reactivation rates after transplantation, viral load, and use of antiviral and antifungal pharmacotherapy.
We will evaluate the safety of infusions with respect to the development of adverse events within the first 12 months post-CTL infusion and the dynamics of cell persistence by T-cell chimerism analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 3rd party CTL infusion | Experimental | Biological: Virus specific CTLsVirus specific CTLs |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Recipients of myeloablative or non-myeloablative allogeneic or solid organ transplantation for any indication.
- Presence of viral reactivation or infection with CMV, Adv or EBV or invasive fungal disease must be present at the time of infusion as determined by:
- Failure of standard therapy as defined by:
- Increase or less than 50% decrease in the EBV viral load in peripheral blood despite use of appropriate therapy as determined by the treating physician which may include:
- Reduction in immunosuppression
Key exclusion criteria (5 listed)
- Use of anti-lymphocyte globulin (ALG, ATG, Campath or other broad spectrum lymphocyte antibody) given in the 4 weeks immediately prior to infusion or planned within 4 weeks after infusion.
- Grade II or greater graft versus host disease within 1 week prior to infusion.
- Prednisone or methylprednisolone at a dose of > 1 mg/kg (or equivalent in other steroid preparations) administered within 72 hours prior to cell infusion.
- ECOG status 4 or Lansky score <30
- Privately insured in or outpatients in New South Wales participating centres (see 12.5 Indemnity issues).
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 CTLsAlso: T cellsVirus specific CTLs will be given to patients with persistent or recurrent viral reactivation after 2 weeks of standard anti-viral therapy | Biological | 3rd party CTL infusion |
Primary outcome
Infusion related safety
Time frame: 1 week
infusion related adverse events
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2016.
- Derived from this study: PubMed 29296867Withers B, Blyth E, Clancy LE, Yong A, Fraser C, Burgess J, Simms R, Brown R, Kliman D, Dubosq MC, Bishop D, Sutrave G, Ma CKK, Shaw PJ, Micklethwaite KP, Gottlieb DJ. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. Blood Adv. 2017 Nov 2;1(24):2193-2205. doi: 10.1182/bloodadvances.2017010223. eCollection 2017 Nov 14.
- Individual participant dataSharing planned: No
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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.
David Gottlieb, MD FRACP contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Virus specific CTLs in people with CMV Infection and EBV, run by University of Sydney at 1 site in Australia.
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 18 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 21 Jul 2016. 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 Australia. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact David Gottlieb, MD FRACP (david.gottlieb@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infusion related safety (time frame: 1 week). 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 NCT02779439, 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 21 Jul 2016.