Adenovirus InfectionPhase 1/2CTL-ADVNCT02851576
Clinical Grade Adenovirus Specific T Cells for Immunotherapy After Allogeneic Stem Cell Transplantation (CTL-ADV)
A Phase 1/2 study testing Infusion of ADV specific T cells in people with Adenovirus Infection, run by Central Hospital, Nancy, France at 1 site in France.
Trial summary
Fourteen patients will be included for infusion of adenovirus-specific T-cells generated by a clinical grade IFN-γ based immunomagnetic isolation from a leukapheresis from their original donor or a haploidentical donor, in case of Umbilical cord blood transplantation, in the event of refractory ADV infection or… Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Adenovirus Infection
- What is being tested?
- Infusion of ADV specific T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteFrance
- Study dates
- Aug 2011to Mar 2015
- 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Study Population : adults or children
- Allogeneic hematopoietic stem cell (bone marrow and peripheral blood stem cell, umbilical cord blood (UCB))
- sibling or matched unrelated donors 10/10 or 9/10 ((M)MUD) or haploidentical donor in case of UCB transplantation
- Within 18 months after HSCT, occurrence of:
- An adenovirus infection without clinical symptoms (except fever with unknown origin) definitively due to this infection, after treatment failure during at least 2 weeks with Cidofovir (5 mg/kg/week).
- To determine ADV infection, 2 consecutive viremia performed at 4 days interval must be higher than viral threshold of 500 copies/mL (with significant increase between these 2 analysis and at least 0, 5 log when the first viremia is equal to 500 cp/mL).
Show all 12Show fewer
- Probable or definitive adenovirus infection after Cidofovir treatment failure, 5 mg/kg/week (according to Wisconsin's criteria)
- and/or renal toxicity or major intolerance to anti-viral drug
- and/or in case Cidofovir is not available in France
- Acute or Chronic GVHD with acute form grade II or less, controlled after 2 lines of treatment at the most.
- Or controlled Chronic GVHD
- Life expectancy > 1 month at the time of inclusion
Who cannot join
- Graft failure
- Derogatory HSCT
- Acute or Chronic GVHD in acute form with grade > II, uncontrolled after 2 lines of immunosuppressive agents.
- Patients with grade > III clinical or biological toxicities (according to OMS classification)
- Chronic GVHD uncontrolled
- Immediate life-threatening
- Patients have not signed informed consent
Trial locations and contacts
1 site in 1 country.
France1 site
Centre Hospitalier Universitaire de Nancy
Vandœuvre-lès-Nancy, 54511
About this study
Official title: Generation of Clinical Grade Adenovirus Specific T Cells for Adoptive Immunotherapy After Allogeneic Stem Cell Transplantation : Clinical Trial
Fourteen patients will be included for infusion of adenovirus-specific T-cells generated by a clinical grade IFN-γ based immunomagnetic isolation from a leukapheresis from their original donor or a haploidentical donor, in case of Umbilical cord blood transplantation, in the event of refractory ADV infection or disease.
Read the detailed description
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has improved over the last decades. However, after HSCT and especially with matched unrelated, cord blood or haploidentical donors, patients often experience a deep immunodeficiency, increasing susceptibility to viral infections. Among them, adenovirus (ADV) systemic infection, often refractory to antiviral treatment, is associated with a high mortality rate up to 50% (even more in children). Viremia monitoring after HSCT has contributed to improve survival allowing the implementation of a pre-emptive anti-viral treatment before any appearance of clinical signs of ADV disease. Nevertheless, no anti-viral drug is authorized for ADV infections, although intravenous (IV) cidofovir seemed to be, up to now, the most efficient. However, nephrotoxicity, especially tubular dysfunction, is often described, requiring hydratation and uroprotection with probenecid and limiting the treatment period.
Meanwhile, adoptive transfer of ADV-specific T cells, prepared with an immunomagnetic clinical grade technology, is becoming an alternative treatment that has already proved feasible, safe and helpful in viral clearance and immune reconstitution related to an in vivo expansion of ADV-specific T cells leading to clinical improvement (Feuchtinger et al, 2006, 2015; Qazim et al, 2013). Our team proposes a multicenter Phase I/II clinical trial with ADV-specific T cells where 14 patients, with refractory ADV infection or disease after unrelated Peripheral blood or umbilical cord blood HSCT, are included.
- Conditions
- Adenovirus Infection
- Being tested
- Infusion of ADV specific T cells
- Keywords
- Adenovirus
- Medical subject headings
- Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of ADV specific T cellsOther
Cell engineering
| Study group | Role | What they receive |
|---|---|---|
| Infusion of ADV specific T cells | Experimental | This one arm study consists in ADV-specific T cell infusion after HSCT from a (M)MUD or, for the first time, from a haploidentical donor for patients having undergone previous UCB transplantation, in the event of refractory ADV infection or disease. Specific anti-ADV immune reconstitution was observed in all patients, and viral load clearance in all but one. Receives: Other: Infusion of ADV specific T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft Versus Hot Disease (GVHD) grade >2
No occurrence of acute Graft Versus Hot Disease (GVHD) grade >2 and/or extensive chronic GVHD and no reactivation or worsening of acute or chronic GVHD during the first month following infusion.
Measured: 1 month
Secondary outcomes (2)
Follow-up of ADV viral load
Follow-up of ADV viral load by quantitative Polymerase Chain Reaction (PCR) : Decrease > 0.5 Log
Measured: 90 days
Follow-up of anti-ADV immune response
Follow-up of anti-ADV immune response in the recipient (developing a specific immune response based on in vivo CTL expansion evaluated by IFN ELISPOT or intracellular cytokine staining).
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2016 (estimated)
- Study startAug 2011
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Adenovirus InfectionStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cécile POCHON, Doctor, Principal investigator, Central Hospital, Nancy, FranceLaurence CLEMENT, Doctor, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02851576
- Sponsor's protocol ID
- 2010-A01029-30
- Acronym
- CTL-ADV
- Status last verified
- Sep 2016
- First submitted
- 28 Jul 2016
- Last updated
- 15 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Aissi-Rothe L, Decot V, Venard V, Jeulin H, Salmon A, Clement L, Kennel A, Mathieu C, Dalle JH, Rauser G, Cambouris C, de Carvalho M, Stoltz JF, Bordigoni P, Bensoussan D. Rapid generation of full clinical-grade human antiadenovirus cytotoxic T cells for adoptive immunotherapy. J Immunother. 2010 May;33(4):414-24. doi: 10.1097/CJI.0b013e3181cc263b.
PubMed 20386465Feucht J, Opherk K, Lang P, Kayser S, Hartl L, Bethge W, Matthes-Martin S, Bader P, Albert MH, Maecker-Kolhoff B, Greil J, Einsele H, Schlegel PG, Schuster FR, Kremens B, Rossig C, Gruhn B, Handgretinger R, Feuchtinger T. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT. Blood. 2015 Mar 19;125(12):1986-94. doi: 10.1182/blood-2014-06-573725. Epub 2015 Jan 23.
PubMed 25617426Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K, Handgretinger R, Peters C, Schuster FR, Beck R, Schumm M, Lotfi R, Jahn G, Lang P. Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. 2006 Jul;134(1):64-76. doi: 10.1111/j.1365-2141.2006.06108.x.
PubMed 16803570Qian C, Campidelli A, Wang Y, Cai H, Venard V, Jeulin H, Dalle JH, Pochon C, D'aveni M, Bruno B, Paillard C, Vigouroux S, Jubert C, Ceballos P, Marie-Cardine A, Galambrun C, Cholle C, Clerc Urmes I, Petitpain N, De Carvalho Bittencourt M, Decot V, Reppel L, Salmon A, Clement L, Bensoussan D. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial. J Hematol Oncol. 2017 May 8;10(1):102. doi: 10.1186/s13045-017-0469-0.
PubMed 28482908
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Generation of Clinical Grade Adenovirus Specific T Cells for Adoptive Immunotherapy After Allogeneic Stem Cell Transplantation : Clinical Trial
- ClinicalTrials.gov ID
- NCT02851576
- Acronym / sponsor ID
- CTL-ADV / 2010-A01029-30
- Conditions
- Adenovirus Infection
- Keywords
- Adenovirus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 1 Aug 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.
Fourteen patients will be included for infusion of adenovirus-specific T-cells generated by a clinical grade IFN-γ based immunomagnetic isolation from a leukapheresis from their original donor or a haploidentical donor, in case of Umbilical cord blood transplantation, in the event of refractory ADV infection or disease.
Detailed description
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has improved over the last decades. However, after HSCT and especially with matched unrelated, cord blood or haploidentical donors, patients often experience a deep immunodeficiency, increasing susceptibility to viral infections. Among them, adenovirus (ADV) systemic infection, often refractory to antiviral treatment, is associated with a high mortality rate up to 50% (even more in children). Viremia monitoring after HSCT has contributed to improve survival allowing the implementation of a pre-emptive anti-viral treatment before any appearance of clinical signs of ADV disease. Nevertheless, no anti-viral drug is authorized for ADV infections, although intravenous (IV) cidofovir seemed to be, up to now, the most efficient. However, nephrotoxicity, especially tubular dysfunction, is often described, requiring hydratation and uroprotection with probenecid and limiting the treatment period.
Meanwhile, adoptive transfer of ADV-specific T cells, prepared with an immunomagnetic clinical grade technology, is becoming an alternative treatment that has already proved feasible, safe and helpful in viral clearance and immune reconstitution related to an in vivo expansion of ADV-specific T cells leading to clinical improvement (Feuchtinger et al, 2006, 2015; Qazim et al, 2013). Our team proposes a multicenter Phase I/II clinical trial with ADV-specific T cells where 14 patients, with refractory ADV infection or disease after unrelated Peripheral blood or umbilical cord blood HSCT, are included.
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 ADV specific T cells | Experimental | Other: Infusion of ADV specific T cellsThis one arm study consists in ADV-specific T cell infusion after HSCT from a (M)MUD or, for the first time, from a haploidentical donor for patients having undergone previous UCB transplantation, in the event of refractory ADV infection or disease. Specific anti-ADV immune reconstitution was observed in all patients, and viral load clearance in all but one. |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Study Population : adults or children
- Allogeneic hematopoietic stem cell (bone marrow and peripheral blood stem cell, umbilical cord blood (UCB))
- sibling or matched unrelated donors 10/10 or 9/10 ((M)MUD) or haploidentical donor in case of UCB transplantation
- An adenovirus infection without clinical symptoms (except fever with unknown origin) definitively due to this infection, after treatment failure during at least 2 weeks with Cidofovir (5 mg/kg/week).
- To determine ADV infection, 2 consecutive viremia performed at 4 days interval must be higher than viral threshold of 500 copies/mL (with significant increase between these 2 analysis and at least 0, 5 log when the first viremia is equal to 500 cp/mL).
Key exclusion criteria (7 listed)
- Graft failure
- Derogatory HSCT
- Acute or Chronic GVHD in acute form with grade > II, uncontrolled after 2 lines of immunosuppressive agents.
- Patients with grade > III clinical or biological toxicities (according to OMS classification)
- Chronic GVHD uncontrolled
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 |
|---|---|---|
| Infusion of ADV specific T cellsCell engineering | Other | Infusion of ADV specific T cells |
Primary outcome
Graft Versus Hot Disease (GVHD) grade >2
Time frame: 1 month
No occurrence of acute Graft Versus Hot Disease (GVHD) grade >2 and/or extensive chronic GVHD and no reactivation or worsening of acute or chronic GVHD during the first month following infusion.
2 secondary outcomes
Follow-up of ADV viral load
Time frame: 90 days
Follow-up of anti-ADV immune response
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2016.
- Background: PubMed 20386465Aissi-Rothe L, Decot V, Venard V, Jeulin H, Salmon A, Clement L, Kennel A, Mathieu C, Dalle JH, Rauser G, Cambouris C, de Carvalho M, Stoltz JF, Bordigoni P, Bensoussan D. Rapid generation of full clinical-grade human antiadenovirus cytotoxic T cells for adoptive immunotherapy. J Immunother. 2010 May;33(4):414-24. doi: 10.1097/CJI.0b013e3181cc263b.
- Background: PubMed 25617426Feucht J, Opherk K, Lang P, Kayser S, Hartl L, Bethge W, Matthes-Martin S, Bader P, Albert MH, Maecker-Kolhoff B, Greil J, Einsele H, Schlegel PG, Schuster FR, Kremens B, Rossig C, Gruhn B, Handgretinger R, Feuchtinger T. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT. Blood. 2015 Mar 19;125(12):1986-94. doi: 10.1182/blood-2014-06-573725. Epub 2015 Jan 23.
- Background: PubMed 16803570Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K, Handgretinger R, Peters C, Schuster FR, Beck R, Schumm M, Lotfi R, Jahn G, Lang P. Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. 2006 Jul;134(1):64-76. doi: 10.1111/j.1365-2141.2006.06108.x.
- Derived from this study: PubMed 28482908Qian C, Campidelli A, Wang Y, Cai H, Venard V, Jeulin H, Dalle JH, Pochon C, D'aveni M, Bruno B, Paillard C, Vigouroux S, Jubert C, Ceballos P, Marie-Cardine A, Galambrun C, Cholle C, Clerc Urmes I, Petitpain N, De Carvalho Bittencourt M, Decot V, Reppel L, Salmon A, Clement L, Bensoussan D. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial. J Hematol Oncol. 2017 May 8;10(1):102. doi: 10.1186/s13045-017-0469-0.
- 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.
Cécile POCHON, Doctor principal investigator
Central Hospital, Nancy, France
Laurence CLEMENT, Doctor principal investigator
University Hospital, Bordeaux
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 Infusion of ADV specific T cells in people with Adenovirus Infection, run by Central Hospital, Nancy, France 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 12 inclusion and 7 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: finished, as of the sponsor's last update on 15 Sep 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Graft Versus Hot Disease (GVHD) grade >2 (time frame: 1 month). 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 NCT02851576, which also lists 4 linked publications.
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 15 Sep 2016.