Extracorporeal Photopheresis (ECP) With Methoxsalen for Chronic Graft Versus Host Disease (cGVHD)

A Randomized Controlled Study of Extracorporeal Photopheresis (ECP) Therapy With UVADEX for the Treatment of Patients With Moderate to Severe Chronic Graft-versus-Host Disease (cGvHD)

Chronic graft-versus-host disease (cGVHD) is a long-lasting complication that can occur after transplants. The transplanted cells seem to fight with the patient's own cells.

Extracorporeal photopheresis (ECP) is a fairly new procedure for cGVHD. The participant gets a port to hook up to a machine. The machine removes the white blood cells, mixes them with a light-sensitive drug, shines light on it, and puts all the blood back in.

This study will find out if patients respond better if they get ECP with methoxsalen, in addition to the pills normally used to treat cGVHD.

Study Overview

• Status: Completed
• Conditions: Chronic Graft Versus Host Disease
• Intervention / Treatment: Drug: ECP Methoxsalen; Drug: Standard of Care

Detailed Description

The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use.

This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment.

Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • General Hospital of Vienna (Medical University of Vienna)
• France
  • Nantes, France
    • CHU de Nantes
  • Paris, France
    • Hospital Saint Louis
  • Paris
    • Saint Antoine, Paris, France, 75571
      • Hopital Saint Antoine
• Germany
  • Cologne, Germany, 50937
    • Universitätsklinik Köln
  • Dresden, Germany, 01309
    • Universitäts-Klinikum Carl Gustav Carus
  • Erlangen, Germany, 91054
    • Universitatsklinikum Erlangen
  • Essen, Germany, 45122
    • Universitatsklinikum Essen
  • Hamburg, Germany, 20246
    • Universitatskrankenhaus Hamburg-Eppendorf
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig AöR
  • Mannheim, Germany, 68167
    • Universitätklinikum Mannheim
  • Munchen, Germany, 81377
    • Medizinische Universitätsklinik
  • Tubingen, Germany, 72076
    • Uniklinik für Kinder und Jugendmedizin
• Hungary
  • Budapest, Hungary, 1097
    • Egyesített Szent István és Szent László Kórház, Gyáli út 5-7,
• Italy
  • Catania, Italy
    • A.O.U. Policlinico- Vittorio Emanuele
  • Genova, Italy
    • Universita de Genova - Ospedale S. Martino
• Spain
  • Barcelona, Spain, 08025
    • Santa Creu I Sant Pau
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Marques de Valdecilla
• United Kingdom
  • Birmingham, United Kingdom
    • University of Birmingham: Queen Elizabeth Hospital
  • London, United Kingdom
    • Royal Marsden Hospital
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • Kings College Hospital
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center, 1430 Tulane Avenue, Rm 7551,
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital,Transplant center
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System of San Antonio

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

To be eligible for inclusion in this trial, the patient must have moderate to severe chronic graft-versus-host disease [defined by the National Institutes of Health (NIH) 2015 Consensus Criteria] that started within 3 years after hematopoietic stem cell transplantation (HSCT).

Exclusion Criteria:

• Is intolerant to corticosteroids or hypersensitive to methoxsalen
• Received certain treatments during time periods disallowed by protocol

• Has infections and/or requires treatment that (per protocol or in the opinion of the investigator) might compromise:

  1. safety and well-being of participant or offspring
  2. safety of study staff
  3. analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ECP Methoxsalen + Standard of Care; Participants receive methoxsalen administered via ECP in addition to standard of care	Drug: ECP Methoxsalen; Methoxsalen delivered by ECP; Other Names: Uvadex; Extracorporeal photopheresis (ECP); Drug: Standard of Care; Tapered prednisone with cyclosporine or tacrolimus via oral administration, consistent with local institutional practice (corticosteroids and cyclosporine A/tacrolimus); Other Names: Reference therapy
Active Comparator: Standard of Care; Participants receive standard of care only	Drug: Standard of Care; Tapered prednisone with cyclosporine or tacrolimus via oral administration, consistent with local institutional practice (corticosteroids and cyclosporine A/tacrolimus); Other Names: Reference therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With an Overall Response at Week 28	Participants with overall response included those with partial response or complete response, according to study staff who did not know which treatment they received (blinded assessment).	Week 28

Collaborators and Investigators

• Sponsor: Mallinckrodt
• Collaborators: Parexel

Publications and helpful links

General Publications

• Jagasia M, Scheid C, Socie G, Ayuk FA, Tischer J, Donato ML, Batai A, Chen H, Chen SC, Chin T, Boodee H, Mitri G, Greinix HT. Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD. Blood Adv. 2019 Jul 23;3(14):2218-2229. doi: 10.1182/bloodadvances.2019000145.

Helpful Links

• Cited article made available by the US National Library of Medicine, National Institutes of Health

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): February 19, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; cGVHD; Methoxsalen; Extracorporeal photopheresis therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Photosensitizing Agents; Dermatologic Agents; Methoxsalen
• Other Study ID Numbers: 10-005; 2010-022780-35 (EudraCT Number)

Plan for Individual participant data (IPD)

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