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

Phase 2

• Conditions: Acute-graft-versus-host Disease
• Interventions: Combination Product: Methoxsalen + ECP device; Drug: Corticosteroids

• Registration Number: NCT03605940
• Lead Sponsor: Central Hospital, Nancy, France

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2018-07
• Study First Submitted: 2018-07-21
• Study First Submitted QC: 2018-07-27
• Last Update Submitted: 2018-07-27
• Study First Posted: 2018-07-30
• Last Update Posted: 2018-07-30
• Study Start: 2018-10-01
• Primary Completion: 2021-04-01
• Study Completion: 2022-04-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 78

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental group	Corticosteroids	corticosteroids + ECP
Experimental group	Methoxsalen + ECP device	corticosteroids + ECP
Contrôl group	Corticosteroids	corticosteroids alone

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
cumulative incidence rate of infections	Month 6 - Month 12
incidence of chronic GVHD	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
gamma globulin number	Month 3 - Month 6 - Month 12
mean of the cumulative dose of steroids	Month 1- Month 2 - Month 3 - Month 6 - Month 12
cumulative incidence of thromboembolic complications	Month 3
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
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