A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma Using a Conditioning Regimen of Fludarabine, Melphalan, and Bortezomib
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Progression Free Survival
研究概览
简要总结
The hypothesis for this study is that the regimen consisting of fludarabine, melphalan and bortezomib improves the progression free survival and the response rate compared to historical controls of fludarabine and melphalan alone.
详细描述
Multiple myeloma is the second most prevalent blood cancer (10%) after non-hodgkin's lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although the peak age of onset of multiple myeloma is 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset.
The historical control 2-year progression-free survival (PFS) is assumed to be 35%. The proposed therapy of fludarabine, melphalan and bortezomib is expected to improve the PFS by 20%.
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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of multiple myeloma
- •Have a suitable related or unrelated donor
- •Age ≥18 but <70 yrs
- •KPS of ≥70%
- •Recovery from complications of previous therapies
排除标准
- •Diagnosis other than multiple myeloma
- •Chemotherapy or radiotherapy within 21 days of initiating treatment in this study
- •Prior dose-intense therapy requiring HSC support within 56 days of initiating treatment in this study
- •Uncontrolled bacterial, viral, fungal or parasitic infections
- •Uncontrolled CNS metastases
- •Known amyloid deposition in heart
- •Organ dysfunction
- •LVEF <40% or cardiac failure not responsive to therapy
- •FVC, FEV1, or DLCO <50% of predicted and/or receiving supplementary continuous oxygen
- •Evidence of hepatic synthetic dysfunction, or total bilirubin >2x or AST >3x ULN
- •Measured creatinine clearance <20 ml/min
- •Sensory peripheral neuropathy grade 4 within 14 days of enrollment
- •Karnofsky score <70% unless a result of bone disease directly caused by myeloma
- •Life expectancy limited by another co-morbid illness
- •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
- •Female subject is pregnant or breast-feeding (women) or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Documented hypersensitivity to fludarabine or melphalan or to bortezomib, boron or mannitol or any components of the formulation
- •Patients unable or unwilling to provide consent
- •Patient has a sustained platelet count of <30 x 10 9/L within 14 days before enrollment
- •Patient has a sustained absolute neutrophil count of <1.0 x10 9/L within 14 days before enrollment
- •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 has to be documented by the investigator as not medically relevant
- •Patient has received other investigational drugs with 14 days before enrollment
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study
研究组 & 干预措施
Fludarabine, Melphalan, Bortezomib
干预措施: Fludarabine monophosphate, melphalan, Bortezomib (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: Subjects will be followed for progression-free survival for at least 36 months
The main primary endpoint of this study is two-year progression free survival. Patients are considered a failure with respect to PFS if they die or experience disease progression or relapse. The time to this event is the time from transplantation to relapse/progression, initiation of non-protocol anti-myeloma therapy, or death from any cause. Subjects alive without confirmed disease progression will be censored at the time of last disease evaluation. Deaths without progression are treated as failures no matter when they occur.
次要结局
- Overall Response Rate(Up to 3 years)
- Overall Survival (OS)(Up to 3 years)