Allogeneic Hematopoietic Stem Cell TransplantationAllo-NK-CMVNCT03294824
Non Randomized Comparative Study With Control
An observational study of Allogeneic Hematopoietic Stem Cell Transplantation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal tolerance. They belong to innate immune cells but they have a link with adaptative immunity. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Allogeneic Hematopoietic Stem Cell Transplantation
- What is being tested?
- blood sample
- How many people
- 90 participants
- Where
- 1 siteFrance
- Study dates
- 27 Sep 2013to Jun 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Allogeneic HSCT for malignant or non malignant hematological disease in adult patients
Who may be able to join
- patients who reactivate CMV or AdV after allogeneic HSCT ;
- Age>18 years; indication for a antiviral treatment:
- at least 1 PCR CMV>1000 copies/ml or 1 PCR ADV>1000 copies/ml or at least 2 ADV PCR positive - sites (stools, throat, urines);
- signed informed consent;
- Control group: allogeneic HSC transplanted patients;
- Age>18 years; no CMV or AdV reactivation ;
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- signed informed consent;
- Healthy donors group: HSC donor;
- Age>18 years;
- signed informed consent
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
Laetitia Souchet, Doctor contact
About this study
Official title: Study of Natural Killer Immunity During Infections With CMV or AdV After Allogeneic Hematopoietic Stem Cells
NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal tolerance. They belong to innate immune cells but they have a link with adaptative immunity. Indeed, after some viral infections such as CMV, Chikungunya, B hepatitis etc, a subset of NKG2C+ NK cells expands and can transfer, in murine models, a " memory " that can better control CMV infections. CMV reactivation is a major cause of morbidity and mortality after allogeneic hematopoietic ste cell transplantation in humans. The aim of this prospective study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of CMV but also Adenovirus after allo HSCT. Peripheral NK cells from 30 and 10 patients who reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and functional studies before and after administration of anti viral drugs) and compared with 30 allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors serologically + for CMV.
Read the detailed description
For both groups: 28ml of peripheral blood samples are collected at different points. Group 1 : before and after anti viral treatment . Control group 2: one point after allo-HSCT; Control group 3: 1 point before transplant. Phenotypical study of NK cells: activating and inhibitory receptors, activation and differentiation's markers. Phenotypical studies of the ligands on infected cells. Genotypic study of KIR receptors (Kirotype); functional studies: polyfunctionality essay (flow cytometry): degranulation CD107a, IFNg, TNFa production).
- Being tested
- blood sample
- Keywords
- NK cells, Cytomegalovirus, adenovirus, Allogeneic transplantation
- Medical subject headings
- Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleOther
peripheral blood samples are collected
| Study group | Role | What they receive |
|---|---|---|
| patients who reactivate CMV or AdV after allogeneic HSCT | allotransplanted patients who reactivated respectively CMV (n=30) and AdV (n=10) Receives: Other: blood sample | |
| Control group: allogeneic HSC transplanted patients | allotransplanted patients who didn't reactivate CMV Receives: Other: blood sample | |
| Healthy donors group | healthy donors serologically + for CMV Receives: Other: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry
CD3-CD56+ NK cells will be analyzed by Flow cytometry with an appropriate monoclonal antibodies (mAb) cocktail: anti-CD3 ,CD56, CD16, CD159a/NKG2A , CD85J; HLA-DR ; CD62L , CD161; KIR2DL1 and KIR3DL1, and KIR2DL2/KIR2DL3.
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic markers and will be compared with healthy donors.
Measured: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells
Polyfunctional assay will test the capacity of NK cells degranulation and production of cytokines when incubated with standard HLA class I negative K562 target cells in the presence of anti-CD107a ,IFN-g, or TNF-a mAb.
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and will be compared with healthy donors.
Measured: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
Secondary outcomes (2)
Effect of CMV and AdV infection compared with healthy donors
The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and functional markers and will be compared with healthy donors.
Measured: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
In vitro Nk cells ligands analyzes on infected cells by CMV
Monocyte are differentiated in macrophage cells and infected by the CMV strain TB40/E. Nk cell ligands will be analyzed on infected cells. NK cells from infected patients post allogenic transplantation will be tested against in vitro infected cells.
Being a model in vitro, it is not possible to determine in advance which ligands will be identified.
Measured: approximately 18 months after Study Completion Date (last participant's last visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2017
- Study start27 Sep 2013
- Primary completionJun 2018 (estimated)
- Study completionJun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allogeneic Hematopoietic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephanie Nguyen Quoc, Doctor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03294824
- Sponsor's protocol ID
- P111107
- Other IDs
- IDRCB
- Acronym
- Allo-NK-CMV
- Status last verified
- May 2018
- First submitted
- 15 Feb 2016
- Last updated
- 29 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Natural Killer Immunity During Infections With CMV or AdV After Allogeneic Hematopoietic Stem Cells
- ClinicalTrials.gov ID
- NCT03294824
- Acronym / sponsor ID
- Allo-NK-CMV / P111107
- Keywords
- NK cells, Cytomegalovirus, adenovirus, Allogeneic transplantation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Sep 2013 (actual)
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 27 Sep 2017 (actual)
- 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.
NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal tolerance. They belong to innate immune cells but they have a link with adaptative immunity. Indeed, after some viral infections such as CMV, Chikungunya, B hepatitis etc, a subset of NKG2C+ NK cells expands and can transfer, in murine models, a " memory " that can better control CMV infections. CMV reactivation is a major cause of morbidity and mortality after allogeneic hematopoietic ste cell transplantation in humans. The aim of this prospective study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of CMV but also Adenovirus after allo HSCT. Peripheral NK cells from 30 and 10 patients who reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and functional studies before and after administration of anti viral drugs) and compared with 30 allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors serologically + for CMV.
Detailed description
For both groups: 28ml of peripheral blood samples are collected at different points. Group 1 : before and after anti viral treatment . Control group 2: one point after allo-HSCT; Control group 3: 1 point before transplant. Phenotypical study of NK cells: activating and inhibitory receptors, activation and differentiation's markers. Phenotypical studies of the ligands on infected cells. Genotypic study of KIR receptors (Kirotype); functional studies: polyfunctionality essay (flow cytometry): degranulation CD107a, IFNg, TNFa production).
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| patients who reactivate CMV or AdV after allogeneic HSCT | – | Other: blood sampleallotransplanted patients who reactivated respectively CMV (n=30) and AdV (n=10) |
| Control group: allogeneic HSC transplanted patients | – | Other: blood sampleallotransplanted patients who didn't reactivate CMV |
| Healthy donors group | – | Other: blood samplehealthy donors serologically + for CMV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Allogeneic HSCT for malignant or non malignant hematological disease in adult patients
Key inclusion criteria (10 listed)
- patients who reactivate CMV or AdV after allogeneic HSCT ;
- Control group: allogeneic HSC transplanted patients;
- Healthy donors group: HSC donor;
Key exclusion criteria (1 listed)
- none
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 |
|---|---|---|
| blood sampleperipheral blood samples are collected | Other | Control group: allogeneic HSC transplanted patients, Healthy donors group, patients who reactivate CMV or AdV after allogeneic HSCT |
Primary outcome
Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry
Time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
CD3-CD56+ NK cells will be analyzed by Flow cytometry with an appropriate monoclonal antibodies (mAb) cocktail: anti-CD3 ,CD56, CD16, CD159a/NKG2A , CD85J; HLA-DR ; CD62L , CD161; KIR2DL1 and KIR3DL1, and KIR2DL2/KIR2DL3. The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic markers and will be compared with healthy donors.
NK cells cytoxicity and cytokines production when incubated with standard HLA class I negative K562 target cells
Time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
Polyfunctional assay will test the capacity of NK cells degranulation and production of cytokines when incubated with standard HLA class I negative K562 target cells in the presence of anti-CD107a ,IFN-g, or TNF-a mAb. The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic and will be compared with healthy donors.
2 secondary outcomes
Effect of CMV and AdV infection compared with healthy donors
Time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"
In vitro Nk cells ligands analyzes on infected cells by CMV
Time frame: approximately 18 months after Study Completion Date (last participant's last visit)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2018.
- 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.
Laetitia Souchet, Doctor contact
Stephanie Nguyen Quoc, Doctor principal investigator
Assistance Publique - Hôpitaux de Paris
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 Allogeneic Hematopoietic Stem Cell Transplantation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 10 inclusion and 1 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 29 May 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stephanie Nguyen Quoc, Doctor (33142162823, stephanie.nguyen-quoc@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nk cells phenotype (activation, differentiation, memory NK cell) and function (cytoxicity and cytokines production) measured by flow cytometry (time frame: Change from "before antiviral treatment", " half treatment" (1 week or 2 week after the beginning of the treatment), 1 month "post treatment" and 3 month "post treatment"). 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 29 May 2018.