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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute-graft-versus-host Disease
• Intervention / Treatment: Combination product: Methoxsalen + ECP device; Drug: Corticosteroids

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marie-Thérèse RUBIO, PU-PH; Phone Number: 0383153282; Email: m.rubio@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; corticosteroids + ECP	Combination product: Methoxsalen + ECP device; 2 sessions per week during 4 weeks and 1 session per week during 8 weeks; Drug: Corticosteroids; 2 mg/kg/day
ACTIVE_COMPARATOR: Contrôl group; corticosteroids alone	Drug: Corticosteroids; 2 mg/kg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2018
• Primary Completion (ANTICIPATED): April 1, 2021
• Study Completion (ANTICIPATED): April 1, 2022

Study Registration Dates

• First Submitted: July 21, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (ACTUAL): July 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 30, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Acute-graft-versus-host Disease; Extracorporal Photopheresis
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Photosensitizing Agents; Dermatologic Agents; Methoxsalen
• Other Study ID Numbers: 2017-005162-22; PSS2017/PCE-aGVHD-RUBIO/VS (OTHER: CHRU Nancy)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No