ECP Combination Study

NCT05052385 | Completed FDA Drug FDA Device

• 1 other identifier: 2019000902
• Study Type: observational
• Target: 319
• Locations: 14 countries
• Sites: 38

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.

Conditions

Steroid Refractory GVHD

Keywords

Steroid refractory GVHD; Extracorporeal photopheresis; Ibrutinib; Ruxolitinib; ECP

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Efficacy of ECP

  up to one year

• Safety of ECP

  Up to one year

• Safety of ECP

  Up to one year

• Efficacy of ECP

  Up to one year

• Efficacy of ECP

  Up to one year

Study Arms (6)

ECP only (aGVHD patients)

Patients treated with ECP and other Standard Of Care treatments (SOC)

Device: Extracorporeal photopheresis

ECP and Ruxolitinib (aGVHD patients)

Patients treated with ECP and Ruxolitinib

Drug: Ruxolitinib; Device: Extracorporeal photopheresis

Ruxolitinib only (aGVHD patients)

Patients treated with Ruxolitinib and other Standard Of Care treatments (SOC)

Drug: Ruxolitinib

ECP only (cGVHD patients)

Patients treated with ECP and other Standard Of Care treatments (SOC)

Device: Extracorporeal photopheresis

ECP and treatment combination (cGVHD patients)

Patients treated with ECP and Ruxolitinib or Ibrutinib

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)

Drug: Ruxolitinib; Drug: Ibrutinib

Interventions

Ruxolitinib DRUG

As per treating physician's decision - non interventional study

ECP and Ruxolitinib (aGVHD patients); ECP and treatment combination (cGVHD patients); Ruxolitinib only (aGVHD patients); Treatment combination only (cGVHD patients)

Extracorporeal photopheresis DEVICE

As per treating physician's decision - non interventional study

ECP and Ruxolitinib (aGVHD patients); ECP and treatment combination (cGVHD patients); ECP only (aGVHD patients); ECP only (cGVHD patients)

Ibrutinib DRUG

As per treating physician's decision - non interventional study

ECP and treatment combination (cGVHD patients); Treatment combination only (cGVHD patients)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• European Society for Blood and Marrow Transplantation: lead
• Mallinckrodt: collaborator

Study Sites (38)

Antwerp University

Antwerp, Belgium

Location

University of Liège

Liège, Belgium

Location

Rigshospitalet

Copenhagen, Denmark

Location

CHRU Angers

Angers, France

Location

CHU de Limoges

Limoges, France

Location

Institut de Cancerologie Lucien Neuwirth

Saint-Etienne, France

Location

Bonn University

Bonn, Germany

Location

University Hospital Essen

Essen, Germany

Location

Universitaetsmedizin Mannheim

Mannheim, Germany

Location

Robert_Bosch_Krankenhaus

Stuttgart, Germany

Location

George Papanicolaou General Hospital

Thessaloniki, Greece

Location

Rambam Medical Center

Haifa, Israel

Location

H SS. Antonio e Biagio

Alessandria, Italy

Location

ASST Papa Giovanni XXIII

Bergamo, Italy

Location

Istituto Clinico Humanitas

Milan, Italy

Location

Ospedale Civile

Pescara, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy

Location

Universita Cattolica S. Cuore

Roma, Italy

Location

S. Bortolo Hospital

Vicenza, Italy

Location

Medical University of Gdansk

Gdansk, Poland

Location

Fundeni Clinical Institute

Bucharest, Romania

Location

First State Pavlov Medical University of St. Petersburg

Saint Petersburg, Russia

Location

ICO-Hospital Universitari Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic

Barcelona, Spain

Location

ICO - Hospital Duran i Reynals

Barcelona, Spain

Location

Hosp. Reina Sofia

Córdoba, Spain

Location

Hospital Univ. Virgen de las Nieves

Granada, Spain

Location

Hospital Regional de Málaga

Málaga, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Skanes University Hospital

Lund, Sweden

Location

Baskent University Hospital

Adana, Turkey (Türkiye)

Location

Gazi University Faculty of Medicine

Ankara, Turkey (Türkiye)

Location

University Hospital Birmingham NHS Trust

Birmingham, United Kingdom

Location

Bristol Royal Hospital for Children

Bristol, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

Christie NHS Trust Hospital

Manchester, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

MeSH Terms

Interventions

ruxolitinib; Photopheresis; ibrutinib

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Olaf Penack, MD

  European Society for Blood and Marrow Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: September 22, 2021
• Study Start: April 13, 2021
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: March 28, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); PL (1); FR (3); DK (1); DE (4); SE (2); TU (2); ES (7); GB (5); RO (1); IL (1); IT (7); GR (1); RU (1)