Viral InfectionPhase 1NCT02456610
Administration of Virus Specific CTLs for the Prophylaxis and Treatment of EBV/CMV Infections After HSCT in China
A Phase 1 study testing CMV/EBV specific CTLs in people with Viral Infection, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
Trial summary
Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients in China. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Viral Infection
- What is being tested?
- CMV/EBV specific CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- May 2015to Aug 2016
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with any type of allogeneic HSCT
- CMV, adenovirus or EBV activation or infection which is defined as below. EBV/CMV reactivation is defined as CMV/EBV DNA levels > 1000 IU/ml for a single test or > 500 IU/ml for two consecutive tests. EBV/CMV related disease were defined as the demonstration of CMV/EBV biopsy specimen or clinical diagnosis through symptoms, signs or radiography.
- Written informed consent and/or signed assent line from patient, parent or guardian
- Positive CMV or EBV serology of the donor
- Absence of severe renal disease (Creatinine > 3x upper limit normal)
- Absence of severe hepatic disease (Bilirubin > 3x upper limit normal, AST > 3x upper limit normal)
- Life expectancy > 30 days
Who cannot join
- Active acute GVHD grades II-IV
- Received donor lymphocytes infusion(DLI) within 30 days
- Received ATG or other immunosuppressive monoclonal antibodies within 30 days
- Uncontrolled acute infections
- Active and relapse of malignancy
- Received steroids treatment more than 0.5 mg/kg/day prednisone
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Affiliated Hospital to Academy of Military Medical Sciences
Beijing, Beijing Municipality, 100071
Zhang Bin, M.D., Ph.D., +86-010-6694-7125, zb307ctc@163.com
Chen Hu, M.D., Ph.D., +86-010-6694-7108, chenhu217@aliyun.com
About this study
Official title: Adoptive Transfer of Peptide Stimulated CMV/EBV Specific Cytotoxic T Lymphocytes to Prevent and Treat EBV/CMV Infections in Patients Post Allogeneic Stem Cell Transplantation in China
Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients in China. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. CMV and EBV specific T cells infusion to immunocompromised patients following HSCT is able to induce a successful anti-viral response. The primary purpose of this study is to determine the safety and efficacy of the infusion of CMV and EBV specific cytotoxic T cells (CTLs) for patients with CMV and EBV reactivation or infection.
Read the detailed description
To generate CMV/EBV specific CTLs, G-CSF mobilized hemopoietic progenitor cell (G-HPC) products or nonmobilized peripheral blood apheresis collectings were stimulated with CMV/EBV specific peptides covering most HLA alleles among Chinese populations. Once the investigators made sufficient numbers of T cells, they tested their ex vivo properties.Then a fraction of CTLs were separated for immediate infusion and the others were frozen for further infusion.
If the donor was available, the donor derived CTLs were started to produce when CMV reactivation was detected by qPCR in recipients peripheral blood. Otherwise, autologous CTLs were used. For patients at high risk of developing CMV/EBV infections after stem cell transplantation, a small part of G-HPC products was extracted for CTLs generation.
- Conditions
- Viral Infection
- Being tested
- CMV/EBV specific CTLs
- Medical subject headings
- Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV/EBV specific CTLsBiological
Patients will receive approximately 1x10e6 CTLs/kg as a single infusion via IV injection and may receive 1 to 8 additional infusions at intervals of one week.
| Study group | Role | What they receive |
|---|---|---|
| Infusion of CMV/EBV specific CTLs | Experimental | Repetitive CTLs infusion to treat CMV/EBV activation and infection Receives: Biological: CMV/EBV specific CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity of adoptive transfer of CMV/EBV specific CTLs(The increase of temperature by 1℃ and/or the appearance of rash within 24h after infusion)
Assessment of acute transfusion toxicity within 24 hours after adoptive CTLs transfer
Measured: 24 hours
Assessment of viral load response to the CTL infusion assessed by CMV/EBV specific PCR of peripheral blood
Assess the effect of the CTL infusion on viral load
Measured: 3 months
Secondary outcomes (3)
The incidence of Ⅱ~Ⅳ°aGVHD within 30 days after the last dose of CTL infusion
Measured: 3 months
Reconstitution of antiviral immunity monitored by flow cytometry
Measured: 6 months
Number of patients with chronic GVHD
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2015 (estimated)
- Study startMay 2015
- Primary completionJul 2016 (estimated)
- Study completionAug 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Viral 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chen Hu, M.D., Ph.D., Principal investigator, Affiliated Hospital to Academy of Military Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02456610
- Sponsor's protocol ID
- 307-CMV/EBV-CTL
- Status last verified
- Feb 2016
- First submitted
- 21 May 2015
- Last updated
- 22 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Transfer of Peptide Stimulated CMV/EBV Specific Cytotoxic T Lymphocytes to Prevent and Treat EBV/CMV Infections in Patients Post Allogeneic Stem Cell Transplantation in China
- ClinicalTrials.gov ID
- NCT02456610
- Acronym / sponsor ID
- 307-CMV/EBV-CTL
- Conditions
- Viral Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical SciencesUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Aug 2016 (estimated)
- First posted
- 28 May 2015 (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.
Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients in China. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. CMV and EBV specific T cells infusion to immunocompromised patients following HSCT is able to induce a successful anti-viral response. The primary purpose of this study is to determine the safety and efficacy of the infusion of CMV and EBV specific cytotoxic T cells (CTLs) for patients with CMV and EBV reactivation or infection.
Detailed description
To generate CMV/EBV specific CTLs, G-CSF mobilized hemopoietic progenitor cell (G-HPC) products or nonmobilized peripheral blood apheresis collectings were stimulated with CMV/EBV specific peptides covering most HLA alleles among Chinese populations. Once the investigators made sufficient numbers of T cells, they tested their ex vivo properties.Then a fraction of CTLs were separated for immediate infusion and the others were frozen for further infusion.
If the donor was available, the donor derived CTLs were started to produce when CMV reactivation was detected by qPCR in recipients peripheral blood. Otherwise, autologous CTLs were used. For patients at high risk of developing CMV/EBV infections after stem cell transplantation, a small part of G-HPC products was extracted for CTLs generation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infusion of CMV/EBV specific CTLs | Experimental | Biological: CMV/EBV specific CTLsRepetitive CTLs infusion to treat CMV/EBV activation and infection |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with any type of allogeneic HSCT
- CMV, adenovirus or EBV activation or infection which is defined as below. EBV/CMV reactivation is defined as CMV/EBV DNA levels > 1000 IU/ml for a single test or > 500 IU/ml for two consecutive tests. EBV/CMV related disease were defined as the demonstration of CMV/EBV biopsy specimen or clinical diagnosis through symptoms, signs or radiography.
- Written informed consent and/or signed assent line from patient, parent or guardian
- Positive CMV or EBV serology of the donor
- Absence of severe renal disease (Creatinine > 3x upper limit normal)
Key exclusion criteria (6 listed)
- Active acute GVHD grades II-IV
- Received donor lymphocytes infusion(DLI) within 30 days
- Received ATG or other immunosuppressive monoclonal antibodies within 30 days
- Uncontrolled acute infections
- Active and relapse of malignancy
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 |
|---|---|---|
| CMV/EBV specific CTLsPatients will receive approximately 1x10e6 CTLs/kg as a single infusion via IV injection and may receive 1 to 8 additional infusions at intervals of one week. | Biological | Infusion of CMV/EBV specific CTLs |
Primary outcome
Toxicity of adoptive transfer of CMV/EBV specific CTLs(The increase of temperature by 1℃ and/or the appearance of rash within 24h after infusion)
Time frame: 24 hours
Assessment of acute transfusion toxicity within 24 hours after adoptive CTLs transfer
Assessment of viral load response to the CTL infusion assessed by CMV/EBV specific PCR of peripheral blood
Time frame: 3 months
Assess the effect of the CTL infusion on viral load
3 secondary outcomes
The incidence of Ⅱ~Ⅳ°aGVHD within 30 days after the last dose of CTL infusion
Time frame: 3 months
Reconstitution of antiviral immunity monitored by flow cytometry
Time frame: 6 months
Number of patients with chronic GVHD
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2016.
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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.
Chen Hu, M.D., Ph.D. principal investigator
Affiliated Hospital to Academy of Military Medical Sciences
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 CMV/EBV specific CTLs in people with Viral Infection, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
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 6 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 22 Feb 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 China. 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 Zhang Bin, M.D., Ph.D. (+86-010-6694-7125, zb307ctc@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity of adoptive transfer of CMV/EBV specific CTLs(The increase of temperature by 1℃ and/or the appearance of rash within 24h after infusion) (time frame: 24 hours). The study lists 2 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 22 Feb 2016.