Extracorporal Photopheresis With UVADEX Plus Standard Steroid Treatment for High Risk Acute Graft-versus-host Disease

NCT04291261 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: MAGIC-HR-ECP
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a single arm phase 2 trial which includes patients with high risk acute GVHD defined as Ann Arbor score 2 or 3. The purpose of the study is to improve the outcome of these patients in terms of response to treatment and treatment related mortality. All patients will receive the study intervention (ECP with Uvadex). The study hypothesis is that the treatment plan will produce a day 28 complete response rate higher than or equal to 52%, which will represent an improvement of 15% compared with the standard of care (37%). The rate of complete response to standard of care treatment is based on observed data in similar patients treated within the Mount Sanai Acute GVHD International Consorium (MAGIC). Patients will be treated for 56 days and followed for one year to also enable evaluation of long term outcome.

Conditions

Acute-graft-versus-host Disease

Keywords

Acute-graft-versus-host Disease; Allogeneic Stem Cell Transplantation; Ann Arbor GvHD Scoring

Outcome Measures

Primary Outcomes (1)

• The proportion of complete response CR (that is, per-cent of patients with skin, liver, and GI GvHD all stage 0) at day 28 of study treatment.

  day 28

Secondary Outcomes (9)

• Overall survival at 1 year

  1 year

• Cumulative incidence of NRM

  6 months and at 1 year

• Overall response rate (complete response + partial response)

  day 28 and day 56

• Cumulative incidence of treatment-refractory GvHD

  day 28

• Cumulative incidence of severe GI GvHD (Grade 3 and 4)

  through study completion, an average of 1 year

Study Arms (1)

Extracorporeal photopheresis (ECP) with Uvadex

OTHER

Patients in this single Arm study all receive the intervention consisting of ECP with Uvadex plus the standard of care treatment which consists of systemic corticosteroids 2mg/kg. Response to treatment will be evaluated on day 28. Patients will receive study treatment till day 56 and thereafter be followed until 1 year.

Drug: Uvadex

Interventions

Uvadex DRUG

Extracorporeal photopheresis (ECP) with Uvadex is scheduled 3x/week in weeks 1+2, 2x/week thereafter till day 28 and 1x/week till day 56

Extracorporeal photopheresis (ECP) with Uvadex

Eligibility Criteria

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

You may qualify if:

• New onset high risk acute GvHD (Ann Arbor score 2/3 as defined in Appendix A) following allogeneic SCT. Any clinical severity in accordance with Glucksberg grade II-IV is eligible.
• Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood). Recipients of non-myeloablative and myeloablative transplants are eligible.
• No prior systemic treatment for acute GvHD except for a maximum of 7 days of methylprednisolone ≤2 mg/kg/day (or IV methylprednisolone equivalent) during the period from initiation of systemic steroid treatment for acute GvHD until study therapy begins. Topical skin steroid treatment and non-absorbable oral steroid treatment for GI GvHD are permissible.
• Age 18 years or older.
• Platelet count \> 25.000 (including platelet support)
• Eastern Coorperative Oncology Group (ECOG) score of 0≤2 unless due to aGvHD
• Negative pregnancy test within 10 days before start of study if the patient is a woman of child-bearing Age
• Direct bilirubin must be \<2 mg/dL unless the elevation is known to be due to Gilbert syndrome or aGvHD within 3 days before screening.
• ALT/SGPT and AST/SGOT must be \<5 x the upper limit of the normal range within 3 days before screening.
• Females/Males who agree to comply with the applicable contraceptive requirements of the protocol.
• Written informed consent from patient.
• Biopsy of acute GvHD target organ is strongly recommended but not required. Enrollment should not be delayed for biopsy or pathology results. Patients who do not enroll within 5 working days of Initiation of systemic steroid treatment for acute GvHD are not permitted to participate

You may not qualify if:

• Progressive or relapsed malignancy
• Uncontrolled active infection
• Patients with chronic GvHD
• History of or current diagnosis of progressive multifocal leukoencephalopathy (PML)
• Pregnant or nursing (lactating) women
• Use of other drugs for the treatment of acute GvHD apart from ongoing GvHD prophylaxis and corticosteroids
• Patients on dialysis
• Patients requiring ventilator support
• Evidence of known infection with human immunodeficiency virus (HIV) or active hepatitis B
• Investigational agent within 30 days of enrollment without approval from the Sponsor/ Investigator (PI). (Off-label use of medication is not considered investigational unless in context of a formal study)
• History of allergic reaction to 8-MOP
• Concomitant diagnosis of malignant melanoma or basal cell carcinoma
• Inability to tolerate extracorporeal volume shifts associated with ECP
• Presence of aphakia
• History of splenectomy

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Therakos: collaborator
• University Medical Center Regensburg: collaborator
• Arbeitskreis Klinische Forschung PD Dr. med. Seiler GmbH: collaborator

Study Sites (4)

Medical University of Graz, Department of Internal Medicine

Graz, 8036, Austria

Location

University Medical Center Hamburg-Eppendorf

Hamburg, Hamburg, 20246, Germany

Location

University Hospital Erlangen

Erlangen, 91054, Germany

Location

University Medical Center Regensburg

Regensburg, 93053, Germany

Location

MeSH Terms

Interventions

Methoxsalen

Intervention Hierarchy (Ancestors)

Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Francis A. Ayuk, Prof. Dr.

  University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: March 2, 2020
• Study Start: May 18, 2020
• Primary Completion: June 24, 2024
• Study Completion: June 1, 2025
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); AU (1)