Clinical trial NCT03605940: A Study Comparing Corticosteroids Alone Versus Corticosteroids and Extracorporal Photopheresis (ECP) as First-line Treatment of Standard II Acute Graft-versus-host Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute-graft-versus-host Disease
Keywords: Acute-graft-versus-host Disease
Extracorporal Photopheresis
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2018-07-30
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Probability of being free of treatment failure (probability of survival without relapse, additional line of treatment for aGVHD and systemic therapy for chronic GVHD)
timeFrame: 6 months
Secondary outcomes:
measure: mean of the cumulative dose of steroids
timeFrame: Month 1- Month 2 - Month 3 - Month 6 - Month 12
measure: cumulative incidence rate of infections
timeFrame: Month 6 - Month 12
measure: cumulative incidence of thromboembolic complications
timeFrame: Month 3
measure: incidence of chronic GVHD
timeFrame: Month 6 - Month 12
measure: severity of chronic GVHD
timeFrame: Month 6 - Month 12
measure: incidence rate of non-relapse mortality
timeFrame: Month 6 - Month 12
measure: incidence of disease relapse
timeFrame: Month 6 - Month 12
measure: disease-free survival
timeFrame: Month 6 - Month 12
measure: overall survival
timeFrame: Month 6 - Month 12
measure: scores of health-related quality of life using the French validated FACT-BMT
timeFrame: Month 3 - Month 6 - Month 12
measure: Total T cells number
timeFrame: Month 3 - Month 6 - Month 12
measure: CD4 T cells number
timeFrame: Month 3 - Month 6 - Month 12
measure: CD8 T cells number
timeFrame: Month 3 - Month 6 - Month 12
measure: B cells number
timeFrame: Month 3 - Month 6 - Month 12
measure: NK cells number
timeFrame: Month 3 - Month 6 - Month 12
measure: gamma globulin number
timeFrame: Month 3 - Month 6 - Month 12
Other outcomes:
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