BrUOG 326: A Phase I Dose-Escalation Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With Bendamustine and Rituximab (BRiM) in Indolent Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
This study evaluates addition of Vincristine Sulfate Liposome Injection (Marqibo®) to the standard regimen of Bendamustine and Rituximab in adult patients with indolent B-cell lymphoma. This is a dose-escalation study.
详细描述
Bendamustine-rituximab is a standard chemotherapy regimen for treatment of many indolent B-cell lymphomas, but most patients experience a recurrence of the lymphoma. Vincristine sulfate has been a traditional component of chemotherapy regimens in non-Hodgkin lymphoma and it is possible that adding it to the bendamustine-rituximab regimen might provide a better quality of remissions or longer duration of remissions with acceptable toxicity.
This is a phase 1, single-center, open-label, single-arm trial in patients with indolent B-cell non-Hodgkin lymphoma otherwise appropriate for bendamustine-rituximab as initial or subsequent line of therapy. Patients will receive the of rituximab and bendamustine in combination with escalating doses of vincristine sulfate liposome injection (Marqibo®). The objective of this study is to assess safety of this combination by establishing the maximum tolerated dose of vincristine sulfate liposome injection (Marqibo®) in the combination.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed indolent B-cell non-Hodgkin lymphoma.
- •Radiological measurable disease.
- •Previous treatment for lymphoma is allowed, with the exception of use of bendamustine within 6 months or any prior use of vincristine sulfate liposome injection
- •Eastern Cooperative Oncology Group performance status 0 or 1;
- •Life expectancy of at least 6 months;
- •Adequate organ and marrow function;
- •Women of child-bearing potential and men must agree to use adequate contraception.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •History of allergic reactions attributed to any drug used in the study.
- •Any lymphoma-directed therapy within 4 weeks.
- •Any prior treatment with vincristine sulfate liposome injection.
- •Prior treatment with bendamustine or vincristine sulfate within 180 days of enrollment.
- •Patients who are receiving any other investigational agents with the exception of endocrine therapy for breast or prostate cancer.
- •Central nervous system involvement.
- •Peripheral sensory or motor neuropathy.
- •History of a demyelinating condition.
- •Positive test for the Human Anti-Chimeric Antibody (HACA).
- •Patients receiving any medications or substances that are strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) enzyme are ineligible.
- •Uncontrolled intercurrent illness.
- •Prisoners.
- •Pregnant or breast-feeding women.
- •Known Human Immunodeficiency Virus (HIV) or active Hepatitis B infection
- •Any prior or active cancer, which in the opinion of the investigator would preclude safe participation in this study.
研究组 & 干预措施
Vincristine sulfate liposome injection 1.8 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 1.8 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 1.8 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 1.95 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 1.95 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 1.95 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 1.98 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 1.98 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 1.98 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 2.04 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 2.04 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 2.04 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 2.10 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 2.10 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 2.10 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 2.14 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 2.14 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 2.14 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 2.19 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 2.19 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 2.19 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 2.22 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 2.22 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 2.22 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
Vincristine sulfate liposome injection 2.24 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Rituximab (Drug)
Vincristine sulfate liposome injection 2.24 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Bendamustine (Drug)
Vincristine sulfate liposome injection 2.24 mg/m^2
Treatment with the combination of rituximab, bendamustine and vincristine sulfate liposome injection will be repeated every 4 weeks for a maximum of 6 cycles. Dose-limiting toxicities will be evaluated during the first cycle of therapy.
干预措施: Vincristine sulfate liposome injection (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: Up to 6 cycles of treatment (approximately 6 months)
Determined as the median of the marginal posterior distribution using data from all available patients
次要结局
- Number of Participants Who Completed Six Cycles of Study Treatment(Up to 6 cycles of treatment (approximately 6 months))
- Response Rate(Up to 6 cycles of treatment (approximately 6 months))
- Complete Response Rate(Up to 6 cycles of treatment (approximately 6 months))