A Phase I Trial of Post-Transplant Bortezomib and High Dose Cyclophosphamide as Graft-Versus-Host Disease (GVHD) Prophylaxis After Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity
研究概览
简要总结
The purpose of this study is to determine if Bortezomib, known commercially as Velcade is safe and tolerated at different dose levels (amounts) with high dose Cyclophosphamide to be used as graft versus host disease prevention after reduced-intensity allogeneic hematopoietic stem cell transplantation.
详细描述
It is hypothesized that the administration of an early and short course cyclophosphamide and bortezomib after allogeneic hematopoietic stem cell transplantationin in the setting of matched related or unrelated donor transplantation using a standard reduced-intensity conditioning regimen is feasible.
The study is a phase I study. The primary objective of the study is to determine the feasibility and safety of increasing doses of bortezomib administered post-transplant in conjunction with fixed high dose cyclophosphamide, also administered post-transplant in the setting of reduced-intensity allogeneic hematopoietic stem cell transplant, as GVHD prophylaxis strategy. Eligible patients will receive a conditioning regimen based on a combination of fludarabine and busulfan with or without rATG.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- 未提供
排除标准
- •Age <18 years
- •Poor performance status (<70%)
- •Active infections
- •Abnormal creatinine clearance <40ml/min
- •Elevated bilirubin >1.5 and ALT and AST .2 times the upper limit of normal
- •Poor ejection fraction <40%
- •Pregnant female.
- •HIV positive
- •Inability to provide informed consent
- •Patient has >/= Grade 2 peripheral neuropathy
- •Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- •Patient has hypersensitivity to bortezomib, boron, or mannitol.
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of 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.
- •Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
研究组 & 干预措施
Cohort 1-Bortezomib (Velcade®)
Bortezomib (Velcade®) 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
干预措施: Cohort 1-Bortezomib (Velcade ®) (Drug)
Cohort 2-Bortezomib (Velcade®)
Bortezomib (Velcade®) 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
干预措施: Cohort 2-Bortezomib (Velcade ®) (Drug)
Cohort 3-Bortezomib (Velcade®)
Bortezomib (Velcade®) 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
干预措施: Cohort 3-Bortezomib (Velcade ®) (Drug)
结局指标
主要结局
Dose Limiting Toxicity
时间窗: Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.
Grade 3 non-hematologic Common Toxicity Criteria toxicity directly related to bortezomib (such as peripheral neuropathy) or Grade 2 or \> hepatic bilirubin Common Toxicity Criteria Graft failure
次要结局
- Engraftment(Assessed daily by laboratory evaluation until engraftment or up to 90 days.)