Clinical trial NCT05052385: ECP Combination 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Steroid Refractory GVHD
Keywords: Steroid refractory GVHD
Extracorporeal photopheresis
Ibrutinib
Ruxolitinib
ECP
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Mallinckrodt
First posted: 2021-09-22
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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

Eligibility criteria: Inclusion Criteria:

Acute GvHD Patients

1. Patients who develop acute SR-GvHD after first HSCT and there is a minimum of 6 months follow up data in the database
2. Patients who initiate treatment with ECP or Ruxolitinib within 60 days of onset of SR aGvHD
3. Grade: II-IV only at time of treatment initiation
4. Patients who are ≥ 18 years at time of treatment initiation

Chronic GvHD Patients

1. Patients who develop chronic SR-GvHD after first HSCT and there is with a minimum of 1 year follow up data in the database
2. Patients who initiate treatment with ECP or Ruxolitinib or Ibrutinib within I year of the onset of SR-cGvHD
3. Severity: moderate to severe only at time of treatment initiation
4. Patients who are ≥ 18 years at time of treatment initiation

Exclusion Criteria:

Acute GvHD

1. Patients on a clinical trial for GvHD for an interventional drug to treat GvHD in the retrospective period
2. Patient is pregnant or breastfeeding
3. Grade I at time of SR GvHD treatment initiation
4. Patients who receive ECP or new treatment as prophylaxis
5. Patients initiating ECP or new treatment later than 60 days from onset on SR-aGvHD
6. Patients \< 18 years at time of treatment initiation

Chronic GvHD

1. Patients on a clinical trial for an interventional drug to treat GvHD in the retrospective period
2. Patient is pregnant or breastfeeding
3. Chronic GvHD : Severity mild at time of SR GvHD treatment initiation
4. Patients who receive ECP or new treatment as prophylaxis
5. Patients initiating ECP or new treatment after 1 year onset of SR-cGvHD
6. Patients \< 18 years at time of treatment initiation

Primary outcomes:
measure: Overall response rate
timeFrame: 3 months
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Efficacy of ECP
timeFrame: up to one year
measure: Safety of ECP
timeFrame: Up to one year
measure: Safety of ECP
timeFrame: Up to one year
measure: Efficacy of ECP
timeFrame: Up to one year
measure: Efficacy of ECP
timeFrame: Up to one year
measure: Efficacy of ECP
timeFrame: Up to one year
measure: Efficacy of ECP
timeFrame: Up to one year
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Antwerp University
city: Liège
country: Belgium
facility: University of Liège
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Angers
country: France
facility: CHRU Angers
city: Limoges
country: France
facility: CHU de Limoges
city: Saint-Étienne
country: France
facility: Institut de Cancerologie Lucien Neuwirth
city: Bonn
country: Germany
facility: Bonn University
city: Essen
country: Germany
facility: University Hospital Essen
city: Mannheim
country: Germany
facility: Universitaetsmedizin Mannheim
city: Stuttgart
country: Germany
facility: Robert_Bosch_Krankenhaus
city: Thessaloníki
country: Greece
facility: George Papanicolaou General Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Alessandria
country: Italy
facility: H SS. Antonio e Biagio
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
city: Pescara
country: Italy
facility: Ospedale Civile
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Universita Cattolica S. Cuore
city: Vicenza
country: Italy
facility: S. Bortolo Hospital
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Saint Petersburg
country: Russian Federation
facility: First State Pavlov Medical University of St. Petersburg
city: Badalona
country: Spain
facility: ICO-Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: ICO - Hospital Duran i Reynals
city: Córdoba
country: Spain
facility: Hosp. Reina Sofia
city: Granada
country: Spain
facility: Hospital Univ. Virgen de las Nieves
city: Málaga
country: Spain
facility: Hospital Regional de Málaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skanes University Hospital
city: Adana
country: Turkey
facility: Baskent University Hospital
city: Ankara
country: Turkey
facility: Gazi University Faculty of Medicine
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Trust
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: London
country: United Kingdom
facility: Kings College Hospital
city: Manchester
country: United Kingdom
facility: Christie NHS Trust Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: European Society for Blood and Marrow Transplantation
name: Olaf Penack, MD
role: PRINCIPAL_INVESTIGATOR
References: