Graft Vs Host Disease
Conditions
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.
Interventions
DRUGUvadex
Uvadex use for ECP
DRUGSteroids
steroids 2 mg/kg/d
Sponsors
Central Hospital, Nancy, France
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| infections | at 6 months from randomization | incidence rate of infections (bacteremia, septicemia, fungal infections, parasite and virus |
| chronic GVHD | at 12 months from randomization | incidence and severity of chronic GVHD |
| steroid cumulative dose | at 6 months from randomization | cumulative dose of steroids over time |
| relapse | at 12 months from randomization | incidence of disease relapse |
| overall survival | at 12 months from randomization | overall survival logrank |
| non-relapse mortality | at 12 months from randomization | non-relapse mortality rate |
Countries
France
Outcome results
None listed