Myfortic - Treatment for Extensive cGvHD

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Graft vs Host Disease

Intervention / Treatment
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* Drug: Myfortic
* Drug: Prednisone and Cyclosporine


Participation Criteria
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Eligibility Criteria
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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 Receiving a standard prophylaxis regimen for acute GvHD: CsA plus methotrexate, or CSA+MMF for NMA, or a T-cell depleted transplant Patient gives written informed consent prior to randomization 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Myfortic<br>Patients in this arm will receive Myfortic + Prednisone + Cyclosporine | Drug: Myfortic<br>* 1440mg twice daily<br>|
| Other: Standard Care/ Placebo<br>In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine | Drug: Prednisone and Cyclosporine<br>* Prednisone and Cyclosporine given according to protocol. The drugs are tapered according to patient response<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| survival without recurrent malignancy |  | 1 year | 
| Overall survival |  | 1 year | 
| cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy |  | 1 year | 
| the cumulative incidence of death without recurrent or malignancy |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GvHD, graft versus host disease, extensive, myfortic