Patients Undergoing Allogeneic Stem Cell TransplantationPhase 1/2NCT02227641
Preventative/Preemptive Adoptive Transfer of Peptide Stimulated CMV/EBV Specific T-cells in Patients After Allogeneic Stem Cell Transplantation
A Phase 1/2 study testing CMV/EBV specific T-cell in people with Patients Undergoing Allogeneic Stem Cell Transplantation, run by University of Erlangen-Nürnberg Medical School at 6 sites in Germany.
Trial summary
In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening complication requiring antiviral treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Patients Undergoing Allogeneic Stem Cell Transplantation
- What is being tested?
- CMV/EBV specific T-cell
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 6 sitesGermany
- Study dates
- Oct 2014to Mar 2017
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Indication for allogeneic stem cell transplantation
- HLA identical donor, related or unrelated, 10/10 match
- Stem cell source: G-SCF mobilized peripheral blood stem cells
- Presence of at least one HLA allele: A0101, A0201, B0702, B0801, B3501, C0702
- Positive EBV serology of the donor
- Positive CMV serology of the donor
- Adequate contraception
Who cannot join
- Donor CMV seronegative
- Donor EBV seronegative
- Stem cell source: bone marrow or cord blood
- Alemtuzumab for conditioning
- Sorror Score >3
- Pregnancy
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Medical Center Augsburg
Augsburg, 86156
Charité University Hospital Berlin
Berlin, 13353
Universitiy Hospital Erlangen
Erlangen, 91054
University of Mainz
Mainz, 55131
University of Munich LMU
Munich, 81377
University of Regensburg
Regensburg, 93053
About this study
Official title: Prospective, Open, Randomized, Two-arm, Controlled, Multicenter Clinical Phase I/IIa Trial to Evaluate the Safety and Efficacy of Adoptive Immunotherapy With Allogeneic CMV/EBV Specific, Peptide Stimulated T-cells (CD3+) for Prevention or Preemptive Therapy of Reactivation of CMV and/or EBV in Patients After Allogeneic, HLA Identical Stem Cell Transplantation
In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening complication requiring antiviral treatment. The underlying problem is a severe suppression of the donors immune system after transplantation into the patient. Herpesviruses such as CMV and EBV persist after primary infection life long in the host and therefore require constant immunological control. This control is largely provided by the T-cell compartment of the immune system. After allogeneic stem cell transplantation the T-cell compartment requires a long time for its reconstitution since only a small fraction of the donor T-cells are transplanted. During this time Herpesviruses can reoccur due to the lack of effective T-cell control.
This study therefore aims at reconstituting the T-cell compartment with CMV and EBV specific T-cells at an early time point after allogeneic stem cell transplantation. It is mainly a phase I study to demonstrate that these in vitro generated T-cells can be applied safely in this patient population. The study also aims at demonstrating the efficacy of CMV/EBV specific T-cells by monitoring viral reactivation and use of antiviral drugs. The hypothesis is, that CMV/EBV specific T-cell can be applied safely and do not result in graft versus host disease and that they successfully prevent reactivation of CMV and EBV after adoptive transfer in patients after allogeneic stem cell transplantation.
- Being tested
- CMV/EBV specific T-cell
- Keywords
- CMV, Cytomegalovirus, EBV, Epstein Barr Virus, virus, T cell, adoptive transfer, transplantation, allogeneic
- Medical subject headings
- Epstein-Barr Virus Infections, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV/EBV specific T-cellBiological
Also called T cell
Peptide stimulated allogeneic T-cells with dual specificity for CMV and EBV
| Study group | Role | What they receive |
|---|---|---|
| Adoptive transfer of CMV/EBV specific T-cells | Experimental | Repetitive adoptive T-cell transfer starting at day 30 after allogeneic stem cell transplantation. Receives: Biological: CMV/EBV specific T-cell |
| Control | No intervention | Observation only. |
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 T-cells
Assessment of acute transfusion toxicity within 24 hours after adoptive T-cell transfer.
Assessment of the development of acute transfusion associated acute graft versus host disease (GvHD) within 28 days after adoptive T-cell transfer
Measured: 1-28 days after adoptive T-cell transfer
Secondary outcomes (4)
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on virus reactivation
Incidence of reactivation of CMV and/or EBV during the observation period assessed by virus specific PCR of peripheral blood.
Measured: During observation period until day 204 post transplantation
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of antiviral therapy
Cumulative dose of Ganciclovir, Valganciclovir, Foscarnet, Cidofovir
Measured: During observation period until day 204 post transplantation
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of Rituximab
Cumulative dose of Rituximab.
Measured: During observation period until day 204 post transplantation
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on T-cell reconstitution
Immunomonitoring of peripheral blood by flow cytometry.
Measured: During observation period until day 204 post transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study startOct 2014
- Primary completionOct 2016
- Study completionMar 2017
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 Patients Undergoing Allogeneic Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by University of Erlangen-Nürnberg Medical SchoolThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Erlangen-Nürnberg Medical School
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, University of Regensburg, Johannes Gutenberg University Mainz, Charite University, Berlin, Germany, University Hospital Augsburg, BayImmuNet Bavarian Immunotherapy Network, German Research Foundation
- Responsible party
- Sponsor
- Investigators
- Armin H Gerbitz, MD, PhD, Study director, Charite University, Berlin, GermanyBernd Spriewald, MD, PhD, Principal investigator, University Hospital ErlangenAnita Kremer, MD,PhD, Principal investigator, University Hospital ErlangenKatja San Niccolo, MD, Principal investigator, University Hospital Erlangen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227641
- Sponsor's protocol ID
- AIT-MULTIVIR-01
- Other IDs
- 2012-004240-30
- Status last verified
- Dec 2020
- First submitted
- 26 Aug 2014
- Last updated
- 14 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gerbitz A, Gary R, Aigner M, Moosmann A, Kremer A, Schmid C, Hirschbuehl K, Wagner E, Hauptrock B, Teschner D, Roesler W, Spriewald B, Tischer J, Moi S, Balzer H, Schaffer S, Bausenwein J, Wagner A, Schmidt F, Brestrich J, Ullrich B, Maas S, Herold S, Strobel J, Zimmermann R, Weisbach V, Hansmann L, Lammoglia-Cobo F, Remberger M, Stelljes M, Ayuk F, Zeiser R, Mackensen A. Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study. Front Immunol. 2023 Oct 30;14:1251593. doi: 10.3389/fimmu.2023.1251593. eCollection 2023.
PubMed 37965339
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Open, Randomized, Two-arm, Controlled, Multicenter Clinical Phase I/IIa Trial to Evaluate the Safety and Efficacy of Adoptive Immunotherapy With Allogeneic CMV/EBV Specific, Peptide Stimulated T-cells (CD3+) for Prevention or Preemptive Therapy of Reactivation of CMV and/or EBV in Patients After Allogeneic, HLA Identical Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT02227641
- Acronym / sponsor ID
- AIT-MULTIVIR-01
- Keywords
- CMV, Cytomegalovirus, EBV, Epstein Barr Virus, virus, T cell, adoptive transfer, transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of Erlangen-Nürnberg Medical SchoolUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, University of Regensburg, Johannes Gutenberg University Mainz, Charite University, Berlin, Germany, University Hospital Augsburg, BayImmuNet Bavarian Immunotherapy Network, German Research Foundation
- Study start
- Oct 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 28 Aug 2014 (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.
In patients after allogeneic stem cell transplantation reactivation of latent herpesviruses such as Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) is a frequent and life threatening complication requiring antiviral treatment. The underlying problem is a severe suppression of the donors immune system after transplantation into the patient. Herpesviruses such as CMV and EBV persist after primary infection life long in the host and therefore require constant immunological control. This control is largely provided by the T-cell compartment of the immune system. After allogeneic stem cell transplantation the T-cell compartment requires a long time for its reconstitution since only a small fraction of the donor T-cells are transplanted. During this time Herpesviruses can reoccur due to the lack of effective T-cell control.
This study therefore aims at reconstituting the T-cell compartment with CMV and EBV specific T-cells at an early time point after allogeneic stem cell transplantation. It is mainly a phase I study to demonstrate that these in vitro generated T-cells can be applied safely in this patient population. The study also aims at demonstrating the efficacy of CMV/EBV specific T-cells by monitoring viral reactivation and use of antiviral drugs. The hypothesis is, that CMV/EBV specific T-cell can be applied safely and do not result in graft versus host disease and that they successfully prevent reactivation of CMV and EBV after adoptive transfer in patients after allogeneic stem cell transplantation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adoptive transfer of CMV/EBV specific T-cells | Experimental | Biological: CMV/EBV specific T-cellRepetitive adoptive T-cell transfer starting at day 30 after allogeneic stem cell transplantation. |
| Control | No intervention | –Observation only. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Indication for allogeneic stem cell transplantation
- HLA identical donor, related or unrelated, 10/10 match
- Stem cell source: G-SCF mobilized peripheral blood stem cells
- Presence of at least one HLA allele: A0101, A0201, B0702, B0801, B3501, C0702
- Positive EBV serology of the donor
Key exclusion criteria (6 listed)
- Donor CMV seronegative
- Donor EBV seronegative
- Stem cell source: bone marrow or cord blood
- Alemtuzumab for conditioning
- Sorror Score >3
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 T-cellAlso: T cellPeptide stimulated allogeneic T-cells with dual specificity for CMV and EBV | Biological | Adoptive transfer of CMV/EBV specific T-cells |
Primary outcome
Toxicity of adoptive transfer of CMV/EBV specific T-cells
Time frame: 1-28 days after adoptive T-cell transfer
Assessment of acute transfusion toxicity within 24 hours after adoptive T-cell transfer. Assessment of the development of acute transfusion associated acute graft versus host disease (GvHD) within 28 days after adoptive T-cell transfer
4 secondary outcomes
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on virus reactivation
Time frame: During observation period until day 204 post transplantation
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of antiviral therapy
Time frame: During observation period until day 204 post transplantation
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on the use of Rituximab
Time frame: During observation period until day 204 post transplantation
Influence of preventative/preemptive adoptive transfer of CMV/EBV specific T-cells on T-cell reconstitution
Time frame: During observation period until day 204 post transplantation
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 14 Dec 2020.
- Derived from this study: PubMed 37965339Gerbitz A, Gary R, Aigner M, Moosmann A, Kremer A, Schmid C, Hirschbuehl K, Wagner E, Hauptrock B, Teschner D, Roesler W, Spriewald B, Tischer J, Moi S, Balzer H, Schaffer S, Bausenwein J, Wagner A, Schmidt F, Brestrich J, Ullrich B, Maas S, Herold S, Strobel J, Zimmermann R, Weisbach V, Hansmann L, Lammoglia-Cobo F, Remberger M, Stelljes M, Ayuk F, Zeiser R, Mackensen A. Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study. Front Immunol. 2023 Oct 30;14:1251593. doi: 10.3389/fimmu.2023.1251593. eCollection 2023.
- Dept. of Medicine 5, Hematology/Oncology, University of ErlangenLink provided by the sponsor.
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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.
Armin H Gerbitz, MD, PhD study director
Charite University, Berlin, Germany
Bernd Spriewald, MD, PhD principal investigator
University Hospital Erlangen
Anita Kremer, MD,PhD principal investigator
University Hospital Erlangen
6 sites 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 CMV/EBV specific T-cell in people with Patients Undergoing Allogeneic Stem Cell Transplantation, run by University of Erlangen-Nürnberg Medical School at 6 sites in Germany.
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: finished, as of the sponsor's last update on 14 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. 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?
Toxicity of adoptive transfer of CMV/EBV specific T-cells (time frame: 1-28 days after adoptive T-cell transfer). 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 NCT02227641, 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 14 Dec 2020.