A Phase II Trial of Daily Low-Dose Interleukin-2 (IL-2) for Steroid-Refractory Chronic Graft-Versus-Host-Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD
研究概览
简要总结
Chronic GVHD is a medical condition that may occur after a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. It is thought that IL-2 may help control chronic GVHD by stopping the donor's immune system from 'rejecting' your body. In this research study, we are looking to see how IL-2 can be used in combination with steroids to treat cGVHD.
详细描述
You will give yourself or be given IL-2 daily through an injection under your skin. You should rotate the injection site, if possible. You will do this once every day for 12 weeks. You will then have 4 weeks off of IL-2. During the first 6 weeks of IL-2, you will continue to take steroids without changing the dose your doctor has set for you while you are on IL-2. After 6 weeks of IL-2 therapy, your doctor may reduce the amount of steroids you take.
While you are on study, a member of the study team will examine you to evaluate your cGVHD. These assessments may include examination of your skin, joints/muscles, eyes, mouth, lungs and gastrointestinal system.
You will have clinic visits for evaluation of toxicity and clinical benefit approximately every 4 weeks. You will also have immunologic assays approximately every 8 weeks. Immunologic assays will measure the effect of IL-2 on immune cells.
You will be on the study for about 16 weeks. You may continue on study treatment for longer if you experience a clinical benefit.
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
- •Recipient of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
- •Steroid refractory cGVHD with systemic therapy onset within the prior 6 months
- •No more than 2 prior lines of cGVHD therapy
- •Estimated life expectancy > 3 months
- •Adequate organ function
排除标准
- •Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
- •Concurrent use of calcineurin-inhibitors plus sirolimus
- •History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
- •Active malignant relapse
- •Active uncontrolled infection
- •Uncontrolled cardiac angina or symptomatic congestive heart failure
- •Organ transplant (allograft) recipient
- •HIV-positive on combination antiretroviral therapy
- •Active hepatitis B or C
- •Pregnant or breast-feeding
研究组 & 干预措施
Interleukin-2
Each study participant will receive daily subcutaneous IL-2 (1 x 106 IU/m2/day) for self-administration for 12 weeks, followed by a 4-week hiatus. IL-2 will be typically administered on an outpatient basis. After completing the 16 week study (12 weeks of IL-2 study treatment and a mandatory 4 weeks off-IL-2), patients experiencing clinical benefit (complete or partial response; as well as minor response not meeting NIH criteria for partial response) with an acceptable toxicity profile will be permitted to continue extended-duration treatment indefinitely at the discretion of the treating physician.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD
时间窗: Baseline, 6 weeks, and 12 weeks
Participants were evaluated according to the cGVHD NIH Consensus criteria at baseline, 6 weeks, and 12 weeks on study. Per cGVHD NIH Consensus criteria, cGVHD involved organ systems are given a grade 0-3 and an overall cGVHD score, from 0-10, is given. Complete Response is defined as resolution of all reversible manifestations in each organ or site of cGVHD. A partial response is defined as an improvement in measure at least one organ or site, or decrease in global ratings by at least a 2-point change on the 10-point scale, without progression measured at any other organ or site. Non-responders have no change in cGVHD meeting criteria for either partial response or disease progression. Progressive disease is defined as an increase in organ or site scales (1-point change on a 3-point scale) or 2- to 3-point increase on the global cGVHD ratings. Clinical worsening of cGVHD is not synonymous with progressive cGVHD per NIH criteria.
次要结局
- Toxicity of 12-week Course of Low-dose SC IL-2 Therapy(12 weeks)
- Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts(16 weeks of study follow-up)
- Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio(16 weeks of study follow-up)
- Overall Survival and Progression-free Survival(2 years from start of IL-2)
- Prednisone Taper With IL-2 Therapy(End of treatment after 16 weeks or most recent follow-up date for patients on extended)
研究者
John Koreth, MD
Principal Investigator
Dana-Farber Cancer Institute