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

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.

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.

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.