COPAVEHDI: Steroids Versus ECP and Steroids as First-line Treatment of Grade II Acute GVHD
Study Details
Study Description
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:
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to be alive
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without relapse of the hematological disease
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without having required a new line of treatment for acute GVHD
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without initiating a systemic treatment for chronic GVHD.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Steroids alone Steroids 2 mg/kg/day |
Drug: Steroids
steroids 2 mg/kg/d
|
| Experimental: ECP + steroids Steroids 2 mg/kg abd ECP x 2 per week for 1 months and once a week for 2 months |
Drug: Uvadex
Uvadex use for ECP
|
Outcome Measures
Primary Outcome Measures
- Freedom from treatment failure [at 6 months from randomization]
To be alive, without disease relapse, without second line treatment for acute GVHD and without systemic treatment for chronic GVHD
Secondary Outcome Measures
- steroid cumulative dose [at 6 months from randomization]
cumulative dose of steroids over time
- infections [at 6 months from randomization]
incidence rate of infections (bacteremia, septicemia, fungal infections, parasite and virus
- chronic GVHD [at 12 months from randomization]
incidence and severity of chronic GVHD
- non-relapse mortality [at 12 months from randomization]
non-relapse mortality rate
- relapse [at 12 months from randomization]
incidence of disease relapse
- overall survival [at 12 months from randomization]
overall survival logrank
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age > 18 years,
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allogeneic hematopoietic stem cell transplantation received (from any type of graft and donor) after malignant or non malignant disease
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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
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patient requiring first line treatment for acute GVHD
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patient able to start PCE therapy in the 3 days after randomization
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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.
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leukocytes > 1.5 G/l, platelets > 30 G/l, hematocrit > 27% (blood transfusion are permitted), based on the last available blood testing results,
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patient with French Health Insurance,
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patient informed about the clinical trial content and organization,
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informed consent form signed.
Exclusion Criteria:
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- Grade 1 acute GVHD,
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acute GVH grade > II or acute GVH with lower gastrointestinal tract or with liver involvement,
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relapse of the hematologic disease at time of acute GVHD,
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uncontrolled ongoing infection at time of inclusion: bacterial or fungal infections, CMV reactivation with increasing CMV viral load,
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HIV positivity or replicative HBV or HCV infection (based on pre-transplant assessment),
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patient with allergy or contraindications to UVADEX, extracorporeal photopheresis, steroids, or posaconazole (see details in the study protocol),
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woman of childbearing age without efficient contraceptive method, pregnancy or breast feeding woman,
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patient with history of profound venous thrombosis in the last 5 years,
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patient included in another acute GVHD prospective clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHRU de Nancy | Vandoeuvre Les Nancy | France | 54511 |
Sponsors and Collaborators
- Central Hospital, Nancy, France
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023-508614-41-00