A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Clinical Activity
研究概览
简要总结
To study the effectiveness of an immunosuppressive drug sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone.
详细描述
The purpose of this trial is to study the effectiveness of an immunosuppressive drug, sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone. Graft versus host disease (GVHD) is a common complication in patients who have received blood or marrow transplantation from a related or unrelated donor. Chronic GVHD occurs approximately 100 days after transplantation and is the result of the donor immune system recognizing the patient's tissues as foreign and creating harmful effects on the patient's organs. We hope the use of sirolimus will decrease the significant disabling effects and deaths caused by chronic GVHD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 13 years
- •Weight ≥ 40 kg.
- •Biopsy or clinical presentation diagnostic of chronic GVHD >100 days following allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has failed prior corticosteroid therapy or corticosteroid taper. In the event that histological confirmation poses undue risk, clinical evaluation is sufficient.
- •Women of child-bearing potential must have a negative pregnancy test before sirolimus administration and agree to use a medically acceptable contraceptive throughout the treatment period until 3 months after discontinuation of sirolimus.
- •Any woman becoming pregnant during the treatment period must discontinue the use of sirolimus.
- •Absolute neutrophil count (ANC) > 1000/mm³, unless receiving G-CSF to maintain neutrophil count > 500/mm³.
- •At the time of initiating sirolimus the cyclosporine trough level is recommended to be < 100 mg/dl and FK506 level is recommended to be < 5 mg/dl. FK506 or cyclosporine is to be discontinued soon after initiation of sirolimus.
- •Karnofsky performance score ≥ 50 during pre-study screening.
- •Written, signed, and dated informed consent
排除标准
- •Uncontrolled systemic infection
- •Unstable disease states (i.e., hepatic failure, ventilatory-dependent respiratory failure, etc.)
- •Serum creatinine ≥ 3.0 mg/dL
- •Platelet count ≤ 50,000/mm³
- •History of Post-transplant microangiopathic hemolytic anemia
- •Uncontrolled hyperlipidemia
- •Use of any investigational drug within 4 weeks of entry into the study
- •Use of methotrexate or antibody therapies within 24 hours of sirolimus administration
- •Inability to tolerate oral therapy for any reason
- •Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening
- •Known hypersensitivity to macrolide antibiotics
研究组 & 干预措施
Sirolimus Therapy
Administration of Sirolimus and Prednisone
干预措施: Sirolimus (Drug)
Sirolimus Therapy
Administration of Sirolimus and Prednisone
干预措施: Prednisone (Drug)
结局指标
主要结局
Clinical Activity
时间窗: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus
Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment
次要结局
- Overall Survival(3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus)
研究者
Laura Johnston
Associate Professor of Medicine
Stanford University