Steroids Versus ECP and Steroids as First-line Treatment of Grade II Acute GVHD (COPAVEHDI)

A Multi-center Randomized Phase II Study Comparing Corticosteroids Alone Versus Corticosteroids and Extracorporeal Photopheresis as First-line Treatment of Grade II Acute Graft-versus-host Disease With Skin Involvement Occuring After Allogeneic Stem Cell Transplantation

The goal of this clinical trial is to compare as a first line of grade II skin acute GVHD sconventional treatment with steroids alone to a combination of steroids and extracoporeal photopheresis (ECP)

The primary end point will compare Freedom from treatment failure at 6 months from randomization as defined by meeting all the following 4 conditions:

• to be alive
• without relapse of the hematological disease
• without having required a new line of treatment for acute GVHD
• without initiating a systemic treatment for chronic GVHD.

Study Overview

• Status: Not yet recruiting
• Conditions: Graft Vs Host Disease
• Intervention / Treatment: Drug: Steroids; Drug: Uvadex

Detailed Description

A multi-center randomized phase II study comparing corticosteroids alone (standard of care) versus corticosteroids and extracorporeal photopheresis as first-line treatment of Grade II acute graft-versus-host disease with skin +/- upper gastrointestinal involvement occurring after allogeneic stem cell transplantation

Corticosteroids will be started at 2 mg/kg in both arms and will be tapered once acute GVHD achieves complete remission according to strict protocol guidelines (-20% of the daily dose per week until 1 mg/kg and then 10 mg twice a day in order to stop steroids within 2 to 3 months from randomization).

Extracorporeal Photopheresis (ECP) will be performed in the experimental arm : 2 sessions/week during 4 weeks then 1 session/week during 8 weeks), i.e. a total of 16 ECP sessions in 12 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Vandoeuvre Les Nancy, France, 54511
    • CHRU de NANCY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years,
• allogeneic hematopoietic stem cell transplantation received (from any type of graft and donor) after malignant or non malignant disease
• patient suffering from Grade II acute GVHD with skin +/- high GI involvement (stage 2-3 skin + upper gastrointestinal tract or skin stage 3) in the 3 months following stem cell transplantation
• patient requiring first line treatment for acute GVHD
• patient able to start PCE therapy in the 3 days after randomization
• validation of the presence of a peripheral or central venous access (its type should be conform to the recommendations described in the Therakos Cellex operator manual), allowing to perform PCE sessions weekly during 3 months. In the absence of appropriate preexisting central line at inclusion, peripheral access will be preferred.
• leukocytes > 1.5 G/l, platelets > 30 G/l, hematocrit > 27% (blood transfusion are permitted), based on the last available blood testing results,
• patient with French Health Insurance,
• patient informed about the clinical trial content and organization,
• informed consent form signed.

Exclusion Criteria:

• - Grade 1 acute GVHD,
• acute GVH grade > II or acute GVH with lower gastrointestinal tract or with liver involvement,
• relapse of the hematologic disease at time of acute GVHD,
• uncontrolled ongoing infection at time of inclusion: bacterial or fungal infections, CMV reactivation with increasing CMV viral load,
• HIV positivity or replicative HBV or HCV infection (based on pre-transplant assessment),
• patient with allergy or contraindications to UVADEX, extracorporeal photopheresis, steroids, or posaconazole (see details in the study protocol),
• woman of childbearing age without efficient contraceptive method, pregnancy or breast feeding woman,
• patient with history of profound venous thrombosis in the last 5 years,
• patient included in another acute GVHD prospective clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Steroids alone; Steroids 2 mg/kg/day	Drug: Steroids; steroids 2 mg/kg/d
Experimental: ECP + steroids; Steroids 2 mg/kg abd ECP x 2 per week for 1 months and once a week for 2 months	Drug: Uvadex; Uvadex use for ECP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from treatment failure	To be alive, without disease relapse, without second line treatment for acute GVHD and without systemic treatment for chronic GVHD	at 6 months from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
steroid cumulative dose	cumulative dose of steroids over time	at 6 months from randomization
infections	incidence rate of infections (bacteremia, septicemia, fungal infections, parasite and virus	at 6 months from randomization
chronic GVHD	incidence and severity of chronic GVHD	at 12 months from randomization
non-relapse mortality	non-relapse mortality rate	at 12 months from randomization
relapse	incidence of disease relapse	at 12 months from randomization
overall survival	overall survival logrank	at 12 months from randomization

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: 2023-508614-41-00

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: No
• Studies a U.S. FDA-regulated device product: No