Graft Versus Host Disease
Conditions
Keywords
Adult patients (≥18 years), first allogeneic stem cell transplantation, first episode of chronic GVHD requiring systemic immunosuppressive therapy
Brief summary
The main objective of the study is to improve the response rate (complete and partial remission) at 12 months after diagnosis of chronic Chronic Graft Versus Host Disease (GVHD) and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.
Interventions
DRUGRituximab
Patients will receive in addition to ciclosporine A and corticosteroids (prednisone) 1 mg/kg/day, Rituximab at 375 mg/m²/infusion once a week for 4 consecutive weeks.
DRUGCiclosporine
DRUGCorticosteroids
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (≥18 years) who have received a first allogeneic stem cell transplantation for a hematological disease * Confirmed diagnosis of first episode of chronic GVHD requiring systemic immunosuppressive therapy. Chronic GVHD diagnosis is defined according to the NIH Working Group Consensus. Chronic GVHD diagnosis will be based on the evaluation of the severity of the different clinical manifestations including : 1. Ocular, oral and mucosal symptoms, 2. Performance status evaluation, 3. Pulmonary function evaluation, 4. Cutaneous evaluation measured by the percentage of extension of manifestations of liche-noid or sclerodermatous aspects, eventually confirmed with a biopsy whenever possible, 5. Evaluation of the musculoskeletal manifestations, especially the amplitude of the rele-vant articulations, 6. Evaluation of liver involvement (Total bilirubin, Transaminases, Phosphatase alcalines and Gamma GT). * Any source of hematopoietic stem cells is authorized. * Any category of conditioning regimen prior to allo-SCT is authorized. * Any type of stem cell donors is authorized. * Signed informed consent. * Any prior GVHD prophylaxis previously used is accepted. * Absence of contra-indications to the use of Rituximab. * Subjects affiliated with an appropriate social security system. * Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the study and for 3 months following the end of the study.
Exclusion criteria
* Patient developing acute GVHD (whether early or "late onset" form) * A "limited" form of chronic GVHD not requiring systemic immunosuppressive therapy * Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment. * GVHD occurring following donor lymphocytes infusion (DLI) * Not the first episode of chronic GVHD needing systemic immunosuppressive therapy * Neutropenia \<500/µL * Second allogeneic stem cell transplant * Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient's death within 1 month after the start of therapy * Severe neurological or psychiatric disorders * Denied informed consent * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate at 12 months | — | Response rate (complete and partial remission) at 12 months after diagnosis of chronic GVHD and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | — | To spare patients from long-term use of corticosteroids (and of their long-term side effects) |
| Treatment failure | — | To document treatment failure-defined as initiation of another immunosuppressive agent |
| Transplant-related mortality | — | To decrease transplant-related mortality (TRM) of infectious and non-infectious origin |
| Quality of life | — | To improve quality of life parameters |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORMohamad MOHTY, Profesor
Hôpital Saint-Antoine (Paris)
STUDY_CHAIRNoël MILPIED, Profesor
University Hospital, Bordeaux
STUDY_CHAIRMauricette MICHALLET, Profesor
Hospices Civils de Lyon
STUDY_CHAIRKarin BILGER, Doctor
CHRU de Strasbourg
STUDY_CHAIROumédaly REMAN, Doctor
CHRU de Caen
STUDY_CHAIRIbrahim YAKOUB-AGHA, Profesor
CHRU de Lille
STUDY_CHAIRDidier BLAISE, Profesor
Institut Paoli-Calmettes
STUDY_CHAIRPatrice CEBALLOS, Doctor
CHU de Montpellier
STUDY_CHAIRPatrice CHEVALLIER, Doctor
Nantes University Hospital
Outcome results
None listed