A Phase I Study of Ultra-Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
研究概览
简要总结
The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.
详细描述
- IL-2 will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels.
- Participants will be seen periodically while they are receiving IL-2. Physical exams and blood tests will be performed weekly for the first two weeks and then every other week until week 8.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
- •Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
- •Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months without complete resolution of signs and symptoms.
- •Stable dose of corticosteroids for 4 weeks prior to enrollment
- •No addition or subtraction of other immunosuppressive medications for 4 weeks prior to enrollment.
- •Adequate bone marrow, renal and hepatic function as outlined in the protocol
- •18 years of age or older
- •ECOG Performance Status of 0-2
排除标准
- •Ongoing prednisone requirement > 1mg/kg/day (or equivalent)
- •Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
- •Concurrent ECP therapy within 4 weeks prior to enrollment
- •Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
- •Donor lymphocyte infusion within 100 days prior to IL-2 therapy
- •Active malignant disease relapse
- •Active, uncontrolled infection
- •Positive serologic test for Hepatitis B or a positive serologic or nucleic acid test for Hepatitis C
- •HIV seropositivity
- •Life expectancy < 3 months
- •Pregnancy or lactation
- •Inability to comply with IL-2 treatment regimen
- •Uncontrolled cardiac angina or symptomatic congestive heart failure
- •Organ transplant (allograft) recipient
研究组 & 干预措施
Interleukin-2
Interleukin-2 (IL-2) will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels:
Dose Level -A 0.3 x 106 (IU/m2/d) Dose Level -B 1 x 106 (IU/m2/d) Dose Level-C 3 x 106 (IU/m2/d)
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
时间窗: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
Three dose levels were evaluated to determine the maximally tolerated dose (MTD): Dose level A: 0.3 x 10\^6 IU/m\^2/day Dose level B: 1.0 x 10\^6 IU/m\^2/day Dose level C: 3.0 x 10\^6 IU/m\^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.
次要结局
- The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.(Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12)
- CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.(Immunological samples taken at study appointments during the 12 week protocol schedule)
- Treg Cell:Tcon Cell Ratio(Immunological samples taken at study appointments during the 12 week protocol schedule)
研究者
John Koreth, MD
Principal Investigator
Dana-Farber Cancer Institute