A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
研究概览
简要总结
The purpose of this research study is to determine the effectiveness of bortezomib (Velcade) plus prednisone for treating chronic graft versus host disease (cGVHD) and the safety of this drug combination in this patient population. Chronic GVHD is a medical condition that may occur after allogeneic stem cell transplantation. The donor's immune system may recognize the participants body (the host) as foreign and attempt to "reject" it. Bortezomib has been used in other research studies, and information from those studies suggests that this drug may help to control the abnormal immune responses that underlie cGVHD.
详细描述
- Each treatment cycle lasts five weeks, during which time participants will come to the clinic to receive bortezomib intravenously once a week for the first 4 weeks. Prednisone will be taken orally on a daily basis and dose reduction may be initiated after 1 cycle of therapy.
- During all treatment cycles, participants will have the following: physical exam and blood work. At the end of cycle 3 (week 15) the participants cGVHD will be evaluated. These assessments may include an eye examination, a skin examination, a pulmonary function test and/or, a flexion assessment test.
- Participants will receive 3 cycles of bortezomib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •100 days or more past stem cell transplantation
- •Recipients of matched or mismatched, related or unrelated adult donor stem cells
- •Must have cGVHD requiring systemic therapy
- •No addition or subtraction of other immunosuppressive medications. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug. However, if cGVHD occurs during a taper of immune suppression, the medication(s) may not be increased back up to therapeutic level, but will continue a the taper dose for the 15 week study duration
- •Adequate bone marrow, hepatic and renal function as outlined in the protocol
- •Does not require hemodialysis
- •18 years of age or older
- •ECOG Performance Status of 0-2 or Karnofsky performance score of 70% or greater
- •Life expectancy of more than 3 months
排除标准
- •Systemic steroid therapy in the 4 weeks prior to enrollment
- •Active malignant disease after transplantation. Complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy will not be considered in this category
- •Active uncontrolled infection
- •Peripheral neuropathy CTC Grade 1 (or greater) with pain in the 4 weeks before enrollment. Other neurological deficits must be reviewed with the study PI prior to study entry
- •Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- •Hypersensitivity to bortezomib, boron, or mannitol
- •Female subject is pregnant or breast-feeding
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study
研究组 & 干预措施
Velcade (bortezomib)
干预措施: bortezomib (Drug)
Velcade (bortezomib)
干预措施: Prednisone (Drug)
结局指标
主要结局
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
时间窗: Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy
Participants had their cGVHD evaluated per NIH consensus criteria: Complete response: resolution of all reversible manifestations of cGVHD. Partial response: a decrease ≥ 1 point on a 3-point organ-specific scale or 2 points or more on a 10-point global scale without progression in any organ sites. Stable disease: no evidence of cGVHD response without evidence of progressive cGVHD. Progressive cGVHD: increase of ≥ 1 point on an organ-specific 3-point scale, addition of a new immunosuppressive agent prior to the completion of 15 weeks of combination therapy, or requirement an increase in the total daily dose of corticosteroids above a participant's baseline corticosteroid dose during the 15-week combined treatment period. Mixed response: a response in primary sites of cGVHD involvement but interval progressive cGVHD in other organs or sites. Responses were not scored for oral or ocular cGVHD, since topical therapies were permitted during the study.
次要结局
- The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD(Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn)
- Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD(After 15 weeks of bortezomib plus prednisone therapy)
- Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy(1 year after the start of study treatment)
- Overall and cGVHD Progression-free Survival by 1 Year After Therapy(2 years)
研究者
John Koreth, MD
Principal Investigator
Dana-Farber Cancer Institute