Infliximab and Basiliximab for Treatment of Steroid Refractory Acute Graft Versus Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 3
- 主要终点
- Complete Response Rate Determination
研究概览
简要总结
Acute Graft Versus Host Disease (GVHD) is a serious medical condition that is a common development after Bone Marrow Transplant (BMT). Acute GVHD happens when the donor cells attack and damage your tissues and organs after transplant.
Acute GVHD often causes: Skin rashes, nausea, vomiting, abdominal pain, diarrhea (may have blood), liver damage that can cause inflammation in the liver or jaundice (yellowing of the skin or eyes), damage to other organs
Steroids are the first line of treatment for acute GVHD. About a quarter of the patients that develop acute GVHD may not respond to steroid and have steroid refractory GVHD (SR-aGVHD). Patients with SR-aGVHD may need other medications. SR-aGVHD, is a potentially life threatening condition. There is no standard treatment and it may not respond to treatment.
The goals of this study are to find out if Infliximab and basiliximab can treat SR-aGVHD.
Participants in this study will receive combination therapy (2 drugs: infliximab and basiliximab) once a week for four weeks.
详细描述
Corticosteroids are the standard initial therapy for Acute GvHD (aGVHD) after HSCT (hematopoietic stem cell transplant aka BMT) and 25-41% patients will respond to prednisone (or methylprednisolone) at a dose of 2mg/kg/day. Complete response of aGvHD is an important predictor of survival; in patients who respond to steroids, survival is around 50%, while it is as low as 11% for non-responders. Patients who do not develop aGvHD are normally discharged by 4-5 weeks after HSCT. However patients with aGvHD may need to be admitted and require prolonged hospitalization. Patients, who do not respond to treatment, usually have worsening skin symptoms, the protracted diarrhea and vomiting leading to severe life threatening dehydration. Secondary bacterial, fungal and/or viral infections are common and they may eventually die of multiorgan failure.
There is no consensus to the definition of steroid refractory (SR) aGvHD, but generally aGvHD is considered to be SR, when there is progression of GvHD after 3 days or no response after 7 days of treatment with 2mg/kg/day of methyl prednisolone. There is no standard of care for such patients and treatment varies from institution to institution. Salvage regimens for SR GvHD have included high dose steroids, antithymocyte globulin (ATG), monoclonal antibodies (infliximab, daclizumab, basiliximab etc.),pentostatin, mesenchymal stem cells and immunotoxins. Generally if the manifestations of aGvHD worsen over 3 days after starting steroids, or if there is no improvement within 5 days, then it is unlikely that a response will be achieved and secondary therapy should be initiated.
High dose steroids have not been associated with any improvement in response rates for SR aGvHD. In a prospective trial comparing 2mg/kg/day with 10mg/kg/day of methylprednisolone in 94 patients with grade II-IV aGvHD, response rates, progression to grade III-IV disease, non- relapse mortality (NRM) and overall survival were similar in both treatment groups. In addition high dose steroids are associated with many acute and long term complications. Hyperglycemia, hypertension, infections, aseptic necrosis and neurological complications are commonly seen.
Outcome of patients with SR aGvHD is poor. Only 7/57 (12%) patients achieved CR (complete Response)after secondary therapy for aGvHD as reported by Weisdorf et al and only 4/45 (9 %) patients who received high dose methylprednisolone as secondary therapy responded. ATG has been extensively used for treatment of SR GvHD and CR rates of 14-20 % have been reported.
Rationale for using Infliximab and Basiliximab:
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
- 6 Months 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any patient with either progressive aGvHD or Steroid Refractory aGvHD after Bone marrow transplant
- •Prophylactic GvHD therapy with cyclosporine, tacrolimus, MMF, or sirolimus can be continued.
- •Patients with late onset acute GvHD will be eligible
- •Patients should have an absolute neutrophil count (ANC) of >500µL
- •Patients with renal dysfunction or veno-occlusive disease are eligible
排除标准
- •Patient should not be getting any other experimental therapy for aGvHD
- •Patients with active uncontrolled life threatening infection (s) from viral, bacterial, fungal or other organisms will be excluded. Patients with HIV infection will be excluded
- •Patients who are pregnant, breast feeding, or if sexually active and unwilling to use effective birth control for the duration of this study will be excluded
- •Patients with NYHA Class III or IV heart failure will be excluded
研究组 & 干预措施
Infliximab and Basiliximab
Other Names:
Simulect Remicade Monoclonal antibody
Participants in this research study will receive combination therapy (2 drugs: Infliximab and Basiliximab)once a week for four weeks. Both drugs will be given through the participant's broviac, port or through a vein in the arm. It will take about 4-5 hours to complete the 2-drug combination therapy each week. Participants will be given pre-medications to help prevent reactions to the study drugs.
Infliximab will be given at a dose of 10mg per Kg per dose. Basiliximab will be given in 10mg doses to patients who weigh less than 35kg. Patients who weigh weigh more than 35kg will receive 20mg doses. Patients will receive both drugs weekly on days 1,8,15 and 22. Each drug will be given 4 times.
干预措施: Infliximab and Basiliximab (Drug)
结局指标
主要结局
Complete Response Rate Determination
时间窗: 28 days
Complete response was defined as complete resolution of all signs and symptoms of GvHD in all organs using the Modified Glucksberg grading of acute graft versus host disease scale. The score used for GvHD grading complete response was "0" in all evaluable organs.
次要结局
未报告次要终点
研究者
Rajinder Bajwa
Rajinder.P.S. Bajwa, MBBS, MD, MRCP Assitant Professor of Pediatrics at Ohio State University Department of Hematology/Oncology/BMT
Nationwide Children's Hospital