A Randomized Double Blinded Placebo-Controlled Phase III Trial Comparing Cyclosporine Plus Steroids With or Without Myfortic as Primary Treatment for Extensive Chronic Graft Versus Host Disease
Overview
- Phase
- Phase 3
- Intervention
- Myfortic
- Conditions
- Graft vs Host Disease
- Sponsor
- European Society for Blood and Marrow Transplantation
- Enrollment
- 34
- Locations
- 7
- Primary Endpoint
- To test whether the addition of Myfortic improves the efficacy of prednisone plus cyclosporine for treatment of newly diagnosed chronic GvHD, as defined by the proportion of patients with efficacy success at 1 year after enrollment.
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study is to determine whether the response to treatment for extensive chronic Graft versus Host Disease (cGvHD)is improved with the addition of myfortic alongside cyclosporine A and prednisone, compared to the reference treatment of cyclosporine A and prednisone alone.
Detailed Description
This clinical trial is a European, multi-center, randomized, double blinded placebo-controlled trial comparing CsA+PDN+MPA versus the reference treatment of CsA+PDN alone + placebo, in patients with extensive chronic GvHD. Randomization will be stratified according to: * Platelet number (low versus high risk) * Source of transplantable cells (marrow versus PBSC versus cord blood) Patients not in progression at 6 weeks post randomization (progression defined as primary failure) will be evaluated for remission (complete or partial) at 3, 6, 9, \& 12 months post randomization
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 - 60
- •Any primary diagnosis requiring treatment by hematopoietic stem cell transplantation
- •Recipient of a single allogeneic stem cell transplant (bone marrow or peripheral blood stem cells, or cord blood) minimum 80 days ago
- •Received a graft from a related or an unrelated donor
- •Conditioning regimen: Myeloablative or non-myeloablative
- •Patients suffering a first episode of extensive chronic GvHD, without recurrent disease
- •The diagnosis of chronic GvHD requires the following:
- •Distinction from acute GvHD
- •Presence of at least one diagnostic clinical sign of chronic GvHD or presence of at least one distinctive sign confirmed by pertinent biopsy or other relevant diagnostic tests
- •Exclusion of other possible diagnoses
Exclusion Criteria
- •Patient age less than 18 years or over 60 years.
- •GvHD prophylaxis by tacrolimus plus methotrexate
- •Delayed onset acute GvHD following NMA or DLI
- •Second allogeneic stem cell transplant
- •Not the first episode of chronic GvHD needing systemic immunosuppressive therapy.
- •Limited chronic GvHD (Seattle criteria, see Appendix 1)
- •Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient's death within 1 week of randomization
- •In the opinion of the investigator, if the patient has significant medical or psychosocial problems or unstable disease status
- •Pregnant or lactating females
- •Known hypersensitivity to mycophenolic acid
Arms & Interventions
Myfortic
Patients in this arm will receive Myfortic + Prednisone + Cyclosporine
Intervention: Myfortic
Standard Care/ Placebo
In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine
Intervention: Prednisone and Cyclosporine
Outcomes
Primary Outcomes
To test whether the addition of Myfortic improves the efficacy of prednisone plus cyclosporine for treatment of newly diagnosed chronic GvHD, as defined by the proportion of patients with efficacy success at 1 year after enrollment.
Time Frame: 1 year
Secondary Outcomes
- the cumulative incidence of death without recurrent or malignancy(1 year)
- The hazard rates of efficacy success between the two arms. Loss of donor chimerism or recurrent malignancy before secondary systemic therapy and before discontinuation of all immunosuppressive meds will be treated as competing risks.(1 year)
- efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity(1 year)
- cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy(1 year)
- Overall survival(1 year)
- survival without recurrent malignancy(1 year)