A Phase I/II Study of Escalating Doses of Bortezomib in Conjunction With High Dose Melphalan as a Conditioning Regimen for Autologous Peripheral Blood Stem Cell Transplantation in Patients With Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- The Maximum Tolerated Dose of Bortezomib (MTD)
研究概览
简要总结
The purpose of this study is to determine the tolerance and potential efficacy of combining dose intense melphalan with escalating doses of bortezomib in patients with multiple myeloma undergoing autologous stem cell transplantation.
详细描述
Multiple myeloma is the second most common hematological malignancy that has affected approximately 40,000 Americans.Conventional chemotherapy has achieved limited control of this disease but studies have reported improved response rates for patients who are treated with dose-intense therapy and autologous hematopoietic stem cell transplantation. This Phase I/II study will investigate the potential of combination therapy of dose-intense melphalan with escalating doses of bortezomib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A confirmed diagnosis of multiple myeloma
- •Show progression of disease after a previous cycle of dose-intense melphalan, or less than 25% decrease in paraprotein measured at 8 weeks after a prior cycle of dose-intense melphalan
- •May have received intervening therapies for disease progression after dose-intense melphalan and enrollment in this protocol
- •Age:18yrs-76yrs at time of melphalan administration
- •Gender: There is no gender restriction
- •Availability of >2x10^6 autologous peripheral blood CD34+ cells/kg or a syngeneic donor meeting eligibility criteria for syngeneic donation
- •Syngeneic transplantation is preferred
- •For patients enrolled in the phase I part of this study, >1x10^6 autologous or syngeneic peripheral blood CD34+ cells/kg remaining in storage as "backup" in case of engraftment failure
- •Recovery from complications of salvage therapy, if administered -
排除标准
- •Diagnosis other than multiple myeloma
- •Chemotherapy or radiotherapy within 28 days of initiating treatment in this study
- •Prior dose-intense therapy 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 <20ml/min
- •Sensory peripheral neuropathy grade 4
- •Karnofsky score<70% unless a result of bone disease directly caused by myeloma
- •Life expectancy limited by another co-morbid illness
- •History of another malignancy in remission <2yrs (other than basal cell carcinoma)
- •Pregnant (women)or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment
- •Documented hypersensitivity to melphalan or bortezomib or any components of the formulation
- •Patients unable or unwilling to provide consent
研究组 & 干预措施
Phase I Cohort - Bortezomib 1 mg/m2
Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Bortezomib 1 mg/m2 (Drug)
Phase I Cohort - Bortezomib 1 mg/m2
Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Melphalan (Drug)
Phase I Cohort - Bortezomib 1.3 mg/m2
Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Bortezomib 1.3 mg/m2 (Drug)
Phase I Cohort - Bortezomib 1.3 mg/m2
Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Melphalan (Drug)
Phase I Cohort - Bortezomib 1.6 mg/m2
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Bortezomib 1.6 mg/m2 (Drug)
Phase I Cohort - Bortezomib 1.6 mg/m2
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Melphalan (Drug)
Phase II Cohort
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Bortezomib 1.6 mg/m2 (Drug)
Phase II Cohort
Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
干预措施: Melphalan (Drug)
结局指标
主要结局
The Maximum Tolerated Dose of Bortezomib (MTD)
时间窗: During dosing of Bortezomib on Day -4 to Day -1 of ASCT
The Maximum Tolerated Dose of Bortezomib (MTD) Will be Defined as the Dose Level Prior to That Resulting in Two Out of Six Patients Experiencing a DLT
次要结局
未报告次要终点