Clinical trial NCT00298324: Myfortic - Treatment for Extensive cGvHD
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Graft vs Host Disease
Keywords: GvHD
graft versus host disease
extensive
myfortic
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: Novartis
First posted: 2006-03-02
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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
* 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

Primary outcomes:
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: 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.
timeFrame: 1 year
measure: efficacy failure, and treatment failure defined as efficacy failure or premature discontinuation of study-drug administration due to toxicity
timeFrame: 1 year
measure: survival without recurrent malignancy
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: cumulative incidence of secondary systemic treatment for cGvHD before recurrent malignancy
timeFrame: 1 year
measure: the cumulative incidence of death without recurrent or malignancy
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital St. Louis
city: Regensburg
country: Germany
facility: University Regensburg
city: Genova
country: Italy
facility: Ospedale San Martino
city: Maastricht
country: Netherlands
facility: University Hospital
city: Valencia
country: Spain
facility: Hospital Clínico Universitario
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
city: Basel
country: Switzerland
facility: University Hospital
city: Ankara
country: Turkey
facility: University Faculty of Medicine
Study officials:
affiliation: Hôptial St Louis, Paris
name: Gérard Socié
role: STUDY_CHAIR
References: