Clinical trial NCT06133192: Steroids Versus ECP and Steroids as First-line Treatment of Grade II Acute GVHD
Official title: A Multi-center Randomized Phase II Study Comparing Corticosteroids Alone Versus Corticosteroids and Extracorporeal Photopheresis as First-line Treatment of Grade II Acute Graft-versus-host Disease With Skin Involvement Occuring After Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Graft Vs Host Disease
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2023-11-15
Enrollment: 42
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Freedom from treatment failure
timeFrame: at 6 months from randomization
Secondary outcomes:
measure: steroid cumulative dose
timeFrame: at 6 months from randomization
measure: infections
timeFrame: at 6 months from randomization
measure: chronic GVHD
timeFrame: at 12 months from randomization
measure: non-relapse mortality
timeFrame: at 12 months from randomization
measure: relapse
timeFrame: at 12 months from randomization
measure: overall survival
timeFrame: at 12 months from randomization
Other outcomes:
Locations:
city: Vandoeuvre Les Nancy
country: France
facility: CHRU de Nancy
Study officials:
References: