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ECP Combination Study

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ClinicalTrials.gov Identifier: NCT05052385
Recruitment Status : Recruiting
First Posted : September 22, 2021
Last Update Posted : September 22, 2021
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
European Society for Blood and Marrow Transplantation

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.


Condition or disease Intervention/treatment
Steroid Refractory GVHD Drug: Ruxolitinib Device: Extracorporeal photopheresis 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

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Study Type : Observational
Estimated Enrollment : 444 participants
Observational Model: Cohort
Time Perspective: Retrospective
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
Actual Study Start Date : April 13, 2021
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine


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

Device: Extracorporeal photopheresis
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
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

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




Primary Outcome Measures :
  1. 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

  2. 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 ]

Secondary Outcome Measures :
  1. Efficacy of ECP [ Time Frame: up to one year ]
    Organ specific response

  2. Safety of ECP [ Time Frame: Up to one year ]
    Incidence of Complications and infections

  3. Safety of ECP [ Time Frame: Up to one year ]
    Steroid sparing effects

  4. Efficacy of ECP [ Time Frame: Up to one year ]
    overall survival

  5. Efficacy of ECP [ Time Frame: Up to one year ]
    Non Relapse Mortality

  6. Efficacy of ECP [ Time Frame: Up to one year ]
    Duration of response

  7. Efficacy of ECP [ Time Frame: Up to one year ]
    Failure-free survival



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05052385


Contacts
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Contact: Jessica Lemaitre +33 1 70 64 24 15 jessica.lemaitre@upmc.fr
Contact: Emmanuelle Polge emmanuelle.polge@upmc.fr

Locations
Show Show 43 study locations
Sponsors and Collaborators
European Society for Blood and Marrow Transplantation
Mallinckrodt
Investigators
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Principal Investigator: Olaf Penack, MD European Society for Blood and Marrow Transplantation
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Responsible Party: European Society for Blood and Marrow Transplantation
ClinicalTrials.gov Identifier: NCT05052385    
Other Study ID Numbers: 2019000902
First Posted: September 22, 2021    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by European Society for Blood and Marrow Transplantation:
Steroid refractory GVHD
Extracorporeal photopheresis
Ibrutinib
Ruxolitinib
ECP