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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Graft Vs Host Disease

Intervention / Treatment
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* Drug: Uvadex
* Drug: Steroids


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |