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

Phase 2

Not yet recruiting

• Conditions: Graft Vs Host Disease
• Interventions: Drug: Steroids; Drug: Uvadex

• Registration Number: NCT06133192
• Lead Sponsor: Central Hospital, Nancy, France

Brief Summary

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.

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 Timeline

• Status Verified: 2023-10
• Study First Submitted: 2023-11-10
• Study First Submitted QC: 2023-11-10
• Last Update Submitted: 2023-11-10
• Study First Posted: 2023-11-15
• Last Update Posted: 2023-11-15
• Study Start: 2024-01
• Primary Completion: 2025-09
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 42

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Steroids alone	Steroids	Steroids 2 mg/kg/day
ECP + steroids	Uvadex	Steroids 2 mg/kg abd ECP x 2 per week for 1 months and once a week for 2 months

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHRU de Nancy; 🇫🇷 Vandoeuvre Les Nancy, France