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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 7
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Myfortic
Patients in this arm will receive Myfortic + Prednisone + Cyclosporine
干预措施: Myfortic (Drug)
Standard Care/ Placebo
In this arm patients will receive Prednisone + Cyclosporine + Placebo or Prednisone + Cyclosporine
干预措施: Prednisone and Cyclosporine (Drug)
结局指标
主要结局
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.
时间窗: 1 year
次要结局
- 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)