ECP Combination Study

Steroid Refractory GVHD Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05052385
• Other study ID #: 2019000902
• Status: Completed
• Start date: April 13, 2021
• Est. completion date: June 15, 2022

Study information

• Verified date: March 2024
• Source: European Society for Blood and Marrow Transplantation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 319
• Est. completion date: June 15, 2022
• Est. primary completion date: June 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Steroid Refractory GVHD

Intervention

Drug:
• Ruxolitinib
As per treating physician's decision - non interventional study

Device:
• Extracorporeal photopheresis
As per treating physician's decision - non interventional study

Drug:
• Ibrutinib
As per treating physician's decision - non interventional study

Locations

Country	Name	City	State
Belgium	Antwerp University	Antwerp
Belgium	University of Liège	Liège
Denmark	Rigshospitalet	Copenhagen
France	CHRU Angers	Angers
France	CHU de Limoges	Limoges
France	Institut de Cancerologie Lucien Neuwirth	Saint-Étienne
Germany	Bonn University	Bonn
Germany	University Hospital Essen	Essen
Germany	Universitaetsmedizin Mannheim	Mannheim
Germany	Robert_Bosch_Krankenhaus	Stuttgart
Greece	George Papanicolaou General Hospital	Thessaloníki
Israel	Rambam Medical Center	Haifa
Italy	H SS. Antonio e Biagio	Alessandria
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	Istituto Clinico Humanitas	Milano
Italy	Ospedale Civile	Pescara
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Universita Cattolica S. Cuore	Roma
Italy	S. Bortolo Hospital	Vicenza
Poland	Medical University of Gdansk	Gdansk
Romania	Fundeni Clinical Institute	Bucharest
Russian Federation	First State Pavlov Medical University of St. Petersburg	Saint Petersburg
Spain	ICO-Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Hospital Clinic	Barcelona
Spain	ICO - Hospital Duran i Reynals	Barcelona
Spain	Hosp. Reina Sofia	Córdoba
Spain	Hospital Univ. Virgen de las Nieves	Granada
Spain	Hospital Regional de Málaga	Málaga
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Skanes University Hospital	Lund
Turkey	Baskent University Hospital	Adana
Turkey	Gazi University Faculty of Medicine	Ankara
United Kingdom	University Hospital Birmingham NHS Trust	Birmingham
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Kings College Hospital	London
United Kingdom	Christie NHS Trust Hospital	Manchester
United Kingdom	Churchill Hospital	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
European Society for Blood and Marrow Transplantation	Mallinckrodt

Countries where clinical trial is conducted

Belgium,  Denmark,  France,  Germany,  Greece,  Israel,  Italy,  Poland,  Romania,  Russian Federation,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	3 months
Primary	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		6 months
Secondary	Efficacy of ECP	Organ specific response	up to one year
Secondary	Safety of ECP	Incidence of Complications and infections	Up to one year
Secondary	Safety of ECP	Steroid sparing effects (decrease of dose or percentage)	Up to one year
Secondary	Efficacy of ECP	overall survival (Percentage at a fixed time)	Up to one year
Secondary	Efficacy of ECP	Non Relapse Mortality	Up to one year
Secondary	Efficacy of ECP	Duration of response	Up to one year
Secondary	Efficacy of ECP	Failure-free survival	Up to one year