Phase II Study of Bortezomib in Combination With Cyclophosphamide and Rituximab for Relapsed/Refractory Mantle Cell Lymphoma
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
- Response Rate
研究概览
简要总结
The goal of this clinical research study is to learn if bortezomib when given in combination with cyclophosphamide and rituximab can help to control mantle cell lymphoma. The safety of this drug combination will also continue to be studied.
详细描述
The Study Drugs:
Bortezomib is designed to block a protein that plays a role in cell function and growth. This may cause cancer cells to die.
Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
Rituximab is designed to attach to lymphoma cells, which may cause them to die.
Study Drug Administration:
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis mantle cell lymphoma and its variants, excluding marginal zone and disease exclusively in the GI system. Patients should have measurable disease based on Cheson Criteria or Bone Marrow/tissue sample positive for mantle cell lymphoma. No prior therapy with a combination of bortezomib, cyclophosphamide and rituximab.
- •Patients with performance status of 2 or less (Zubrod).
- •Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl unless due to lymphoma; absolute neutrophil count (ANC) >1000/mm^3 and platelets >100,000/mm^3 unless due to lymphoma.
- •Cardiac ejection fraction 50% or greater.
- •Patients must be willing to receive transfusions of blood products.
- •Signed consent form.
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Female subject is either post-menopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent form through 30 days after the last dose of VELCADE, or agree to completely abstain from heterosexual intercourse.
- •Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
排除标准
- •Human immunodeficiency virus (HIV) infection.
- •Central nervous system (CNS) involvement.
- •Patient has a platelet count of < 100 K (eg <30 x 10^9/L for studies with bortezomib alone) within 14 days before enrollment.
- •Patient has an absolute neutrophil count of ANC (eg <1.0 x 10^9/L for studies with bortezomib alone)> within 14 days before enrollment.
- •Patient has > 1.5 times Total Bilirubin
- •Patient has a calculated or measured creatinine clearance of < 20 mL/minute creatinine clearance (eg <20 mL/minute for studies with bortezomib alone) > within 14 days before enrollment.
- •Patient has >/= Grade 2 peripheral neuropathy 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 hypersensitivity to bortezomib, boron or mannitol.
- •Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- •Participation in clinical trials with other investigational agents not included in this trial, within 14 days the start of this trial and throughout the duration of this trial.
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
- •Concurrent or previous malignancy whose prognosis is poor (< 90% probability of survival at 5 years).
研究组 & 干预措施
Bortezomib with Cyclophosphamide and Rituximab
Bortezomib 1.3 mg/m^2 intravenously (IV) on Days 1, 4, 8, and 11 of the cycle; Cyclophosphamide 300 mg/m^2 IV every 12 hours on Days 2, 3, and 4, and Rituximab 375 mg/m^2 IV on Day 1. Mesna 600 mg/m^2 for 3 days, G-CSF 5 micrograms/kg subcutaneously daily for 7 days after last dose of Bortezomib. Cycles repeated every 21 days for up to six cycles.
干预措施: Bortezomib (Drug)
Bortezomib with Cyclophosphamide and Rituximab
Bortezomib 1.3 mg/m^2 intravenously (IV) on Days 1, 4, 8, and 11 of the cycle; Cyclophosphamide 300 mg/m^2 IV every 12 hours on Days 2, 3, and 4, and Rituximab 375 mg/m^2 IV on Day 1. Mesna 600 mg/m^2 for 3 days, G-CSF 5 micrograms/kg subcutaneously daily for 7 days after last dose of Bortezomib. Cycles repeated every 21 days for up to six cycles.
干预措施: Rituximab (Drug)
Bortezomib with Cyclophosphamide and Rituximab
Bortezomib 1.3 mg/m^2 intravenously (IV) on Days 1, 4, 8, and 11 of the cycle; Cyclophosphamide 300 mg/m^2 IV every 12 hours on Days 2, 3, and 4, and Rituximab 375 mg/m^2 IV on Day 1. Mesna 600 mg/m^2 for 3 days, G-CSF 5 micrograms/kg subcutaneously daily for 7 days after last dose of Bortezomib. Cycles repeated every 21 days for up to six cycles.
干预措施: Cyclophosphamide (Drug)
Bortezomib with Cyclophosphamide and Rituximab
Bortezomib 1.3 mg/m^2 intravenously (IV) on Days 1, 4, 8, and 11 of the cycle; Cyclophosphamide 300 mg/m^2 IV every 12 hours on Days 2, 3, and 4, and Rituximab 375 mg/m^2 IV on Day 1. Mesna 600 mg/m^2 for 3 days, G-CSF 5 micrograms/kg subcutaneously daily for 7 days after last dose of Bortezomib. Cycles repeated every 21 days for up to six cycles.
干预措施: Mesna (Drug)
Bortezomib with Cyclophosphamide and Rituximab
Bortezomib 1.3 mg/m^2 intravenously (IV) on Days 1, 4, 8, and 11 of the cycle; Cyclophosphamide 300 mg/m^2 IV every 12 hours on Days 2, 3, and 4, and Rituximab 375 mg/m^2 IV on Day 1. Mesna 600 mg/m^2 for 3 days, G-CSF 5 micrograms/kg subcutaneously daily for 7 days after last dose of Bortezomib. Cycles repeated every 21 days for up to six cycles.
干预措施: G-CSF (Drug)
结局指标
主要结局
Response Rate
时间窗: Evaluation of disease after 2 cycles (approximately 6 weeks).
Response rate to regimen defined as the percentage of number of complete response or partial response in total number of participants treated. The response assessed after the first 2 cycles. Response (complete and partial remission) according to International Workshop Response Criteria for Non-Hodgkin's Lymphoma: A complete response is the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is regression of measurable disease and no new sites of disease. Stable disease is failure to attain a complete response/partial response or progressive disease. A cycle is 21 days with 6-8 cycles administered depending on response.
次要结局
未报告次要终点