Phase II Study of First Line Treatment of Chronic Graft Versus Host Disease With the Association of Ciclosporine, Corticosteroids and Rituximab
Overview
- Phase
- Phase 2
- Intervention
- Rituximab
- Conditions
- Graft Versus Host Disease
- Sponsor
- Nantes University Hospital
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Response rate at 12 months
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
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 :
- •Ocular, oral and mucosal symptoms,
- •Performance status evaluation,
- •Pulmonary function evaluation,
- •Cutaneous evaluation measured by the percentage of extension of manifestations of liche-noid or sclerodermatous aspects, eventually confirmed with a biopsy whenever possible,
- •Evaluation of the musculoskeletal manifestations, especially the amplitude of the rele-vant articulations,
- •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.
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
Arms & Interventions
Rituximab, ciclosporine and corticosteroids
As soon as the diagnosis of chronic GVHD requiring systemic immunosuppressive therapy is confirmed, 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.Rituximab should be administered within 14 days of starting prednisone. Follow-up dates for response assessment and laboratory tests relate to the date of Rituximab infusion.Patients having a partial response after the 1st cycle of Rituximab will be eligible to receive a second cycle of 4 infusions during 4 weeks. A delay of 8 weeks (from the first infusion of Rituximab) will be observed between the two cycles of Rituximab therapy.Patients who relapse after an initial treatment with one cycle of 4 infusions of Rituximab will be eligible to receive a second cycle of Rituximab therapy.
Intervention: Rituximab
Rituximab, ciclosporine and corticosteroids
As soon as the diagnosis of chronic GVHD requiring systemic immunosuppressive therapy is confirmed, 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.Rituximab should be administered within 14 days of starting prednisone. Follow-up dates for response assessment and laboratory tests relate to the date of Rituximab infusion.Patients having a partial response after the 1st cycle of Rituximab will be eligible to receive a second cycle of 4 infusions during 4 weeks. A delay of 8 weeks (from the first infusion of Rituximab) will be observed between the two cycles of Rituximab therapy.Patients who relapse after an initial treatment with one cycle of 4 infusions of Rituximab will be eligible to receive a second cycle of Rituximab therapy.
Intervention: Ciclosporine
Rituximab, ciclosporine and corticosteroids
As soon as the diagnosis of chronic GVHD requiring systemic immunosuppressive therapy is confirmed, 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.Rituximab should be administered within 14 days of starting prednisone. Follow-up dates for response assessment and laboratory tests relate to the date of Rituximab infusion.Patients having a partial response after the 1st cycle of Rituximab will be eligible to receive a second cycle of 4 infusions during 4 weeks. A delay of 8 weeks (from the first infusion of Rituximab) will be observed between the two cycles of Rituximab therapy.Patients who relapse after an initial treatment with one cycle of 4 infusions of Rituximab will be eligible to receive a second cycle of Rituximab therapy.
Intervention: Corticosteroids
Outcomes
Primary Outcomes
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 Outcomes
- Number of participants with adverse events as a measure of safety and tolerability
- Treatment failure
- Transplant-related mortality
- Quality of life