ECP Combination Study

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.

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.

Study Overview

• Status: Completed
• Conditions: Steroid Refractory GVHD
• Intervention / Treatment: Device: Extracorporeal photopheresis; Drug: Ruxolitinib; Drug: Ibrutinib

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 Type: Observational
• Enrollment (Actual): 319

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ECP only (aGVHD patients); Patients treated with ECP and other Standard Of Care treatments (SOC)	Device: Extracorporeal photopheresis; As per treating physician's decision - non interventional study
ECP and Ruxolitinib (aGVHD patients); Patients treated with ECP and Ruxolitinib	Device: Extracorporeal photopheresis; As per treating physician's decision - non interventional study; Drug: Ruxolitinib; As per treating physician's decision - non interventional study
Ruxolitinib only (aGVHD patients); Patients treated with Ruxolitinib and other Standard Of Care treatments (SOC)	Drug: Ruxolitinib; As per treating physician's decision - non interventional study
ECP only (cGVHD patients); Patients treated with ECP and other Standard Of Care treatments (SOC)	Device: Extracorporeal photopheresis; As per treating physician's decision - non interventional study
ECP and treatment combination (cGVHD patients); Patients treated with ECP and Ruxolitinib or Ibrutinib	Device: Extracorporeal photopheresis; As per treating physician's decision - non interventional study; Drug: Ruxolitinib; As per treating physician's decision - non interventional study; Drug: Ibrutinib; As per treating physician's decision - non interventional study
Treatment combination only (cGVHD patients); Patients treated with Ibrutinib and/or Ruxolitinib and other Standard Of Care treatments (SOC)	Drug: Ruxolitinib; As per treating physician's decision - non interventional study; Drug: Ibrutinib; As per treating physician's decision - non interventional study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: European Society for Blood and Marrow Transplantation
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Olaf Penack, MD, European Society for Blood and Marrow Transplantation

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ruxolitinib; Ibrutinib; ECP; Extracorporeal photopheresis; Steroid refractory GVHD
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Ibrutinib
• Other Study ID Numbers: 2019000902

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No