A Study Comparing Corticosteroids Alone Versus Corticosteroids and Extracorporal Photopheresis (ECP) as First-line Treatment of Standard II Acute Graft-versus-host Disease

Study Overview
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Brief Summary
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Acute graft versus host-disease remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. The incidence of grade II to IV acute GVHD ranges from 30 to 50% of the patients transplanted. Steroids remain the standard first line treatment for acute GVHD. Prolonged exposure to steroids is associated to increased risk of infections and of osteoporosis, osteonecrosis and alteration of growth in children. Thus, reducing steroid exposure in order to reduce treatment-related morbidity is another important goal in the management of standard risk aGVHD. Extracoporeal photopheresis (ECP) is active in controlling steroid refractory or dependent acute GVHD. Hypothesis: In this study, the team hypothesizes that addition of ECP to first line treatment with 2 mg/kg steroids of standard risk grade II aGVHD can reduce steroid exposure by increasing the probability of 6 month FFTF including absence of systemic steroids for chronic GVHD.

Official Title
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A Multi-center Randomized Phase II Study Comparing Corticosteroids Alone Versus Corticosteroids and Extracorporal Photopheresis (ECP) as First-line Treatment of Standard Risk Grade II Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

Conditions
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Acute-graft-versus-host Disease

Intervention / Treatment
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* Combination Product: Methoxsalen + ECP device
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years ; Having received an allogeneic stem cell transplantation for any malignant or non-malignant hemopathy and whatever the type of donor and graft. with grade II acute GVHD with skin involvement (stage 1-3 skin +/- stage 1 gastro intestinal) in the 3 months following the allogeneic stem cell transplantation acute GVHD in the first line treatment validation of the presence of peripheral or central venous access allowing to perform 2 ECP per week during 3 months. In the absence of a pre-existing and adpated central catheter at the time of inclusion, peripheral venous access will be preferred Leucocytes > 1.5 G/L Platelets > 30 G/L, Haematocrite > 27% (allowed transfusions) Patient affiliated to a French Social Security regimen information consent form signed. Exclusion Criteria: acute GVHD of grade I acute GVHD of grade > II progressive hematologic disease at inclusion uncontrolled ongoing infection at time of inclusion: bacterial or fungal infections, increasing CMV viral load. patient with HIV positivity or replicative HBV or HCV infection Contraindications for UVADEX / photopheresis / stéroids / posaconazole / heparin Patient with a history of deep venous thrombosis Pregnancy Women of child bearing potentiel not using contaception

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 |
| --- | --- |
| Experimental: Experimental group<br>corticosteroids + ECP | Combination Product: Methoxsalen + ECP device<br>* 2 sessions per week during 4 weeks and 1 session per week during 8 weeks<br>Drug: Corticosteroids<br>* 2 mg/kg/day<br>|
| Active Comparator: Contrôl group<br>corticosteroids alone | Drug: Corticosteroids<br>* 2 mg/kg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of being free of treatment failure (probability of survival without relapse, additional line of treatment for aGVHD and systemic therapy for chronic GVHD) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean of the cumulative dose of steroids |  | Month 1- Month 2 - Month 3 - Month 6 - Month 12 | 
| cumulative incidence rate of infections |  | Month 6 - Month 12 | 
| cumulative incidence of thromboembolic complications |  | Month 3 | 
| incidence of chronic GVHD |  | Month 6 - Month 12 | 
| severity of chronic GVHD |  | Month 6 - Month 12 | 
| incidence rate of non-relapse mortality |  | Month 6 - Month 12 | 
| incidence of disease relapse |  | Month 6 - Month 12 | 
| disease-free survival |  | Month 6 - Month 12 | 
| overall survival |  | Month 6 - Month 12 | 
| scores of health-related quality of life using the French validated FACT-BMT |  | Month 3 - Month 6 - Month 12 | 
| Total T cells number |  | Month 3 - Month 6 - Month 12 | 
| CD4 T cells number |  | Month 3 - Month 6 - Month 12 | 
| CD8 T cells number |  | Month 3 - Month 6 - Month 12 | 
| B cells number |  | Month 3 - Month 6 - Month 12 | 
| NK cells number |  | Month 3 - Month 6 - Month 12 | 
| gamma globulin number |  | Month 3 - Month 6 - Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute-graft-versus-host Disease, Extracorporal Photopheresis