Steroid Refractory GVHDNCT05052385
ECP Combination Study
An observational study of Steroid Refractory GVHD, run by European Society for Blood and Marrow Transplantation at 38 sites in 14 countries.
Trial summary
Extracorporeal photopheresis (ECP) offers an alternative to standard immunosuppression and shows an immunomodulatory rather than an immunosuppressive effect, which is associated with less toxicities and side effects. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Steroid Refractory GVHD
- What is being tested?
- Ruxolitinib, Extracorporeal photopheresis and Ibrutinib
- Type of treatment
- Medical device
- How many people
- 319 participants
- Where
- 38 sitesin 14 countries
- Study dates
- 13 Apr 2021to 15 Jun 2022
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Acute GvHD patients with HSCT who have failed steroids and developed SR-GvHD and are treated with either ECP or/and Ruxolitinib. Patients with HSCT who have developed chronic GvHD and failed to respond to steroids (SR-cGvHD) and are treated with either ECP or/and Ruxolitinib or/and Ibrutinib.
Who may be able to join
- Acute GvHD Patients
- Patients who develop acute SR-GvHD after first HSCT and there is a minimum of 6 months follow up data in the database
- Patients who initiate treatment with ECP or Ruxolitinib within 60 days of onset of SR aGvHD
- Grade: II-IV only at time of treatment initiation
- Patients who are ≥ 18 years at time of treatment initiation
- Chronic GvHD Patients
Show all 10Show fewer
- Patients who develop chronic SR-GvHD after first HSCT and there is with a minimum of 1 year follow up data in the database
- Patients who initiate treatment with ECP or Ruxolitinib or Ibrutinib within I year of the onset of SR-cGvHD
- Severity: moderate to severe only at time of treatment initiation
- Patients who are ≥ 18 years at time of treatment initiation
Who cannot join
- Acute GvHD
- Patients on a clinical trial for GvHD for an interventional drug to treat GvHD in the retrospective period
- Patient is pregnant or breastfeeding
- Grade I at time of SR GvHD treatment initiation
- Patients who receive ECP or new treatment as prophylaxis
- Patients initiating ECP or new treatment later than 60 days from onset on SR-aGvHD
Show all 14Show fewer
- Patients < 18 years at time of treatment initiation
- Chronic GvHD
- Patients on a clinical trial for an interventional drug to treat GvHD in the retrospective period
- Patient is pregnant or breastfeeding
- Chronic GvHD : Severity mild at time of SR GvHD treatment initiation
- Patients who receive ECP or new treatment as prophylaxis
- Patients initiating ECP or new treatment after 1 year onset of SR-cGvHD
- Patients < 18 years at time of treatment initiation
Trial locations and contacts
38 sites in 14 countries.
38 sites in 14 countries
Italy7 sites
H SS. Antonio e Biagio
Alessandria
ASST Papa Giovanni XXIII
Bergamo
Istituto Clinico Humanitas
Milan
Ospedale Civile
Pescara
Azienda Ospedaliero Universitaria Pisana
Pisa
Universita Cattolica S. Cuore
Roma
S. Bortolo Hospital
Vicenza
Spain7 sites
ICO-Hospital Universitari Germans Trias i Pujol
Badalona
Hospital Clinic
Barcelona
ICO - Hospital Duran i Reynals
Barcelona
Hosp. Reina Sofia
Córdoba
Hospital Univ. Virgen de las Nieves
Granada
Hospital Regional de Málaga
Málaga
Hospital Universitario Virgen del Rocío
Seville
United Kingdom5 sites
University Hospital Birmingham NHS Trust
Birmingham
Bristol Royal Hospital for Children
Bristol
Kings College Hospital
London
Christie NHS Trust Hospital
Manchester
Churchill Hospital
Oxford
Germany4 sites
Bonn University
Bonn
University Hospital Essen
Essen
Universitaetsmedizin Mannheim
Mannheim
Robert_Bosch_Krankenhaus
Stuttgart
France3 sites
CHRU Angers
Angers
CHU de Limoges
Limoges
Institut de Cancerologie Lucien Neuwirth
Saint-Etienne
Sweden2 sites
Sahlgrenska University Hospital
Gothenburg
Skanes University Hospital
Lund
Turkey (Türkiye)2 sites
Baskent University Hospital
Adana
Gazi University Faculty of Medicine
Ankara
Russia1 site
First State Pavlov Medical University of St. Petersburg
Saint Petersburg
About this study
Official title: Multi-centre Retrospective Study to Describe the Use and Outcomes of ECP in Combination With New Treatment Protocols in Acute and Chronic GvHD
Extracorporeal photopheresis (ECP) offers an alternative to standard immunosuppression and shows an immunomodulatory rather than an immunosuppressive effect, which is associated with less toxicities and side effects. Additionally ECP has been shown to allow tapering of steroids and immunosuppressant agents which should be a goal of GvHD therapy.
ECP has been used for the management of GvHD since first described in 1994 and as its use has continued over the decades. The treatment was incorporated into a number of guidelines as a second line therapy in steroid refractory or steroid dependent GvHD patients. As well as being used in addition and after steroids, it is also used in combination with CNI Inhibitors, MMF and other immunosuppressant agents.
Read more
However, despite the current widespread use of ECP in the treatment of patients with GvHD, clinical data from randomized studies is limited and small prospective and retrospective trials are the main evidence base .This is also the case for other commonly used immunosuppressant agents, which have been used in GvHD since ECP was introduced.
The systematic review concluded that ECP is an effective therapy for oral, skin, and liver SR-cGVHD, with modest activity in lung and gastrointestinal SR-cGVHD.
In the USA Ibrutinib is the only FDA approved agent for second line cGvHD therapy once steroid therapy has failed and Ruxolitinib had been approved in the USA for the treatment of steroid refractory GvHD.
While studies have shown the effectiveness and safety of ECP in GvHD treatment, there is limited data to show how it is being used in combination with the recently approved agents.
Using existing registry data targeting centres where the newer agents are being used and enhancing the capture of treatment data we believe we can undertake a larger scale study, which will include the new treatment protocols. The aim of the current study is to improve the evidence basis on the potential benefit of ECP use as treatment of GVHD.
Read the detailed description
This is a Registry Based Study (RBS) designed to collect data on the treatment behaviour of acute and chronic GvHD after HSCT. The data collection will be based on the EBMT registry, which so far consists of two questionnaires (Forms A and B), mainly covering the primary disease diagnostics, the status before and at HSCT, the type of HSCT (donor status, preparative regimen etc) and the survival status. With a new questionnaire Form C, which will be similar in design as the current forms used in the registry, we aim at collecting more information and additional data on GvHD characteristics and treatment (schedule, combination, disease states) for both chronic and acute GvHD EBMT will work with the selected sites to facilitate the collection of additional data as specified in section 4.
The data collected will all be retrospective and include up to 3 years of data covering 2017 onwards, from onset of GvHD that has failed to respond to steroids with a minimum data follow up of 6 months for acute and 1 year for chronic. Centres will be asked to select patients that meet the inclusion criteria and fill in Form C retrospectively. The amount of additional data required will depend on whether the centre selected fills in the more detailed Form B or the more minimum data set in Form A.
Criteria for centre selection will be based on:
- Centres that have expressed a willingness to participate in the study through a feasibility questionnaire that was sent out prior to the study or via Email confirmation
- Centres who have responded through the feasibility questionnaire
- Centres where there is prior knowledge of use of both Ruxolitinib/Ibrutinib and ECP or have responded as such in the feasibility questionnaire
- Conditions
- Steroid Refractory GVHD
- Being tested
- Ruxolitinib, Extracorporeal photopheresis, Ibrutinib
- Keywords
- Steroid refractory GVHD, Extracorporeal photopheresis, Ibrutinib, Ruxolitinib, ECP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
As per treating physician's decision - non interventional study
Extracorporeal photopheresisDevice
As per treating physician's decision - non interventional study
IbrutinibDrug
As per treating physician's decision - non interventional study
| Study group | Role | What they receive |
|---|---|---|
| ECP only (aGVHD patients) | Patients treated with ECP and other Standard Of Care treatments (SOC) Receives: Device: Extracorporeal photopheresis | |
| ECP and Ruxolitinib (aGVHD patients) | Patients treated with ECP and Ruxolitinib Receives: Drug: Ruxolitinib; Device: Extracorporeal photopheresis | |
| Ruxolitinib only (aGVHD patients) | Patients treated with Ruxolitinib and other Standard Of Care treatments (SOC) Receives: Drug: Ruxolitinib | |
| ECP only (cGVHD patients) | Patients treated with ECP and other Standard Of Care treatments (SOC) Receives: Device: Extracorporeal photopheresis | |
| ECP and treatment combination (cGVHD patients) | Patients treated with ECP and Ruxolitinib or Ibrutinib Receives: Drug: Ruxolitinib; Device: Extracorporeal photopheresis; Drug: Ibrutinib | |
| Treatment combination only (cGVHD patients) | Patients treated with Ibrutinib and/or Ruxolitinib and other Standard Of Care treatments (SOC) Receives: Drug: Ruxolitinib; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Partial or Complete response according to NIH/Glucksberg classification) at 3 months for acute GvHD since start of targeted* treatment for SR-GvHD
Measured: 3 months
Overall response rate (Partial or Complete response according to NIH/Glucksberg classification) at 6 months for chronic GvHD since start of targeted* treatment for SR-GvHD
Measured: 6 months
Secondary outcomes (7)
Efficacy of ECP
Organ specific response
Measured: up to one year
Safety of ECP
Incidence of Complications and infections
Measured: Up to one year
Safety of ECP
Steroid sparing effects (decrease of dose or percentage)
Measured: Up to one year
Efficacy of ECP
overall survival (Percentage at a fixed time)
Measured: Up to one year
Efficacy of ECP
Non Relapse Mortality
Measured: Up to one year
Efficacy of ECP
Duration of response
Measured: Up to one year
Efficacy of ECP
Failure-free survival
Measured: Up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2021
- Study start13 Apr 2021
- Primary completion15 Jun 2022
- Study completion15 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Steroid Refractory GVHDStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 319 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Society for Blood and Marrow Transplantation
- Sponsor type
- Research network
- Collaborators
- Mallinckrodt
- Responsible party
- Sponsor
- Investigators
- Olaf Penack, MD, Principal investigator, European Society for Blood and Marrow Transplantation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05052385
- Sponsor's protocol ID
- 2019000902
- Status last verified
- Mar 2024
- First submitted
- 8 Jul 2021
- Last updated
- 28 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-centre Retrospective Study to Describe the Use and Outcomes of ECP in Combination With New Treatment Protocols in Acute and Chronic GvHD
- ClinicalTrials.gov ID
- NCT05052385
- Acronym / sponsor ID
- 2019000902
- Conditions
- Steroid Refractory GVHD
- Keywords
- Steroid refractory GVHD, Extracorporeal photopheresis, Ibrutinib, Ruxolitinib, ECP
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 319 participants (actual)
- Lead sponsor
- European Society for Blood and Marrow TransplantationResearch network
- Collaborators
- Mallinckrodt
- Study start
- 13 Apr 2021 (actual)
- Primary completion
- 15 Jun 2022 (actual)
- Study completion
- 15 Jun 2022 (actual)
- First posted
- 22 Sep 2021 (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.
Extracorporeal photopheresis (ECP) offers an alternative to standard immunosuppression and shows an immunomodulatory rather than an immunosuppressive effect, which is associated with less toxicities and side effects. Additionally ECP has been shown to allow tapering of steroids and immunosuppressant agents which should be a goal of GvHD therapy.
ECP has been used for the management of GvHD since first described in 1994 and as its use has continued over the decades. The treatment was incorporated into a number of guidelines as a second line therapy in steroid refractory or steroid dependent GvHD patients. As well as being used in addition and after steroids, it is also used in combination with CNI Inhibitors, MMF and other immunosuppressant agents.
However, despite the current widespread use of ECP in the treatment of patients with GvHD, clinical data from randomized studies is limited and small prospective and retrospective trials are the main evidence base .This is also the case for other commonly used immunosuppressant agents, which have been used in GvHD since ECP was introduced.
The systematic review concluded that ECP is an effective therapy for oral, skin, and liver SR-cGVHD, with modest activity in lung and gastrointestinal SR-cGVHD.
In the USA Ibrutinib is the only FDA approved agent for second line cGvHD therapy once steroid therapy has failed and Ruxolitinib had been approved in the USA for the treatment of steroid refractory GvHD.
While studies have shown the effectiveness and safety of ECP in GvHD treatment, there is limited data to show how it is being used in combination with the recently approved agents.
Using existing registry data targeting centres where the newer agents are being used and enhancing the capture of treatment data we believe we can undertake a larger scale study, which will include the new treatment protocols. The aim of the current study is to improve the evidence basis on the potential benefit of ECP use as treatment of GVHD.
Detailed description
This is a Registry Based Study (RBS) designed to collect data on the treatment behaviour of acute and chronic GvHD after HSCT. The data collection will be based on the EBMT registry, which so far consists of two questionnaires (Forms A and B), mainly covering the primary disease diagnostics, the status before and at HSCT, the type of HSCT (donor status, preparative regimen etc) and the survival status. With a new questionnaire Form C, which will be similar in design as the current forms used in the registry, we aim at collecting more information and additional data on GvHD characteristics and treatment (schedule, combination, disease states) for both chronic and acute GvHD EBMT will work with the selected sites to facilitate the collection of additional data as specified in section 4.
The data collected will all be retrospective and include up to 3 years of data covering 2017 onwards, from onset of GvHD that has failed to respond to steroids with a minimum data follow up of 6 months for acute and 1 year for chronic. Centres will be asked to select patients that meet the inclusion criteria and fill in Form C retrospectively. The amount of additional data required will depend on whether the centre selected fills in the more detailed Form B or the more minimum data set in Form A.
Criteria for centre selection will be based on:
- Centres that have expressed a willingness to participate in the study through a feasibility questionnaire that was sent out prior to the study or via Email confirmation
- Centres who have responded through the feasibility questionnaire
- Centres where there is prior knowledge of use of both Ruxolitinib/Ibrutinib and ECP or have responded as such in the feasibility questionnaire
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| ECP only (aGVHD patients) | – | Device: Extracorporeal photopheresisPatients treated with ECP and other Standard Of Care treatments (SOC) |
| ECP and Ruxolitinib (aGVHD patients) | – | Drug: Ruxolitinib, Device: Extracorporeal photopheresisPatients treated with ECP and Ruxolitinib |
| Ruxolitinib only (aGVHD patients) | – | Drug: RuxolitinibPatients treated with Ruxolitinib and other Standard Of Care treatments (SOC) |
| ECP only (cGVHD patients) | – | Device: Extracorporeal photopheresisPatients treated with ECP and other Standard Of Care treatments (SOC) |
| ECP and treatment combination (cGVHD patients) | – | Drug: Ruxolitinib, Device: Extracorporeal photopheresis, Drug: IbrutinibPatients treated with ECP and Ruxolitinib or Ibrutinib |
| Treatment combination only (cGVHD patients) | – | Drug: Ruxolitinib, Drug: IbrutinibPatients treated with Ibrutinib and/or Ruxolitinib and other Standard Of Care treatments (SOC) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Acute GvHD patients with HSCT who have failed steroids and developed SR-GvHD and are treated with either ECP or/and Ruxolitinib. Patients with HSCT who have developed chronic GvHD and failed to respond to steroids (SR-cGvHD) and are treated with either ECP or/and Ruxolitinib or/and Ibrutinib.
Key inclusion criteria (10 listed)
- Acute GvHD Patients
- Patients who develop acute SR-GvHD after first HSCT and there is a minimum of 6 months follow up data in the database
- Patients who initiate treatment with ECP or Ruxolitinib within 60 days of onset of SR aGvHD
- Grade: II-IV only at time of treatment initiation
- Patients who are ≥ 18 years at time of treatment initiation
Key exclusion criteria (14 listed)
- Acute GvHD
- Patients on a clinical trial for GvHD for an interventional drug to treat GvHD in the retrospective period
- Patient is pregnant or breastfeeding
- Grade I at time of SR GvHD treatment initiation
- Patients who receive ECP or new treatment as prophylaxis
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 |
|---|---|---|
| RuxolitinibAs per treating physician's decision - non interventional study | Drug | ECP and Ruxolitinib (aGVHD patients), ECP and treatment combination (cGVHD patients), Ruxolitinib only (aGVHD patients), Treatment combination only (cGVHD patients) |
| Extracorporeal photopheresisAs per treating physician's decision - non interventional study | Device | ECP and Ruxolitinib (aGVHD patients), ECP and treatment combination (cGVHD patients), ECP only (aGVHD patients), ECP only (cGVHD patients) |
| IbrutinibAs per treating physician's decision - non interventional study | Drug | ECP and treatment combination (cGVHD patients), Treatment combination only (cGVHD patients) |
Primary outcome
Overall response rate
Time frame: 3 months
Partial or Complete response according to NIH/Glucksberg classification) at 3 months for acute GvHD since start of targeted* treatment for SR-GvHD
Overall response rate (Partial or Complete response according to NIH/Glucksberg classification) at 6 months for chronic GvHD since start of targeted* treatment for SR-GvHD
Time frame: 6 months
7 secondary outcomes
Efficacy of ECP
Time frame: up to one year
Safety of ECP
Time frame: Up to one year
Safety of ECP
Time frame: Up to one year
Efficacy of ECP
Time frame: Up to one year
Efficacy of ECP
Time frame: Up to one year
Efficacy of ECP
Time frame: Up to one year
Efficacy of ECP
Time frame: Up to one year
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 28 Mar 2024.
- 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.
Olaf Penack, MD principal investigator
European Society for Blood and Marrow Transplantation
38 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Steroid Refractory GVHD, run by European Society for Blood and Marrow Transplantation at 38 sites in 14 countries.
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 14 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 28 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in Italy, Spain, United Kingdom, Germany, France and 9 more countries. 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?
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?
Overall response rate (time frame: 3 months). 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 28 Mar 2024.