Carfilzomib, Rituximab, and Dexamethasone (CaRD) in Waldenstrom's Macroglobulinemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Overall Response Rate
研究概览
简要总结
Carfilzomib is a drug that has shown anti-tumor activity by inhibiting the proteasome within the cell, which is responsible for degrading or breaking down a wide variety of proteins. Carfilzomib has not been approved by the FDA.
Rituximab and dexamethasone are often used to treat Waldenstrom's Macroglobulinemia (WM), alone or in combination with other drugs. Combinations with rituximab, dexamethasone and proteasome inhibitors, like carfilzomib, show high levels of activity in WM patients.
In this research study, the investigators are testing the safety and efficacy of Carfilzomib when used along with Rituximab and Dexamethasone as a possible treatment for Waldenstrom's Macroglobulinemia.
详细描述
If you take part in this research study, you will receive Carfilzomib and dexamethasone as an infusion on Days 1, 2, 8, and 9 for Cycles 1-6. You will then have a Rituximab infusion on Days 2 and 9. Each cycles lasts 21 days. After completing Cycle 6 and if you are eligible, there will be a 2 month break before the maintenance phase is started. During this break, you will have a study visit with a physical exam, blood tests, and a bone marrow biopsy. If you continue to the maintenance phase, you will receive Carfilzomib and Dexamethasone on Days 1 and 2 and Rituximab on Day 2 of Cycles 1-8. Each cycle will continue to last 21 days, but will take place every 2 months. Infusions will last between 2-6 hours.
During all cycles you will have a physical exam and you will be asked questions about your general health and specific questions about any problems that you might be having and any medications you may be taking. Blood tests will also be done at each Cycle visit, and you will complete a questionnaire. Bone marrow and CT scan will only be repeated at physician discretion when appropriate and in order to ensure your response to treatment.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Waldenstrom's Macroglobulinemia
- •Symptomatic disease
- •Measurable disease
- •Life expectancy of greater than 12 weeks
- •Adequate organ and marrow function
- •CD20 positive based on any previous performed bone marrow immunohistochemistry or flow cytometric analysis
- •Disease free of prior malignancies for >/= 5 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
排除标准
- •More than one prior therapy
- •Previous therapy with a proteasome inhibitor or rituximab
- •Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Currently receiving treatment for any malignancy
- •Major surgery within 21 days prior to study entry
- •Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to study entry
- •Uncontrolled hypertension or uncontrolled diabetes
- •Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to study entry
- •Known history of allergy to Captisol
- •Receiving any other study agents
- •Known brain metastases
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib, rituximab, and/or dexamethasone
- •Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or lactating
- •HIV-positive on combination antiretroviral therapy
研究组 & 干预措施
Treatment Arm
Carfilzomib, dexamethasone, rituximab
干预措施: Dexamethasone (Drug)
Treatment Arm
Carfilzomib, dexamethasone, rituximab
干预措施: Carfilzomib (Drug)
Treatment Arm
Carfilzomib, dexamethasone, rituximab
干预措施: Rituximab (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: 4 years
Overall Response Rate= Minor response (\>25%-50% reduction in serum IgM from baseline + Partial Response (\>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (\>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
Neuropathy Incidence Rate
时间窗: 3 years
Number and percentage of participants who experienced neuropathy attributable to CaRD therapy
Time to Progression
时间窗: 4 years
Progression-free survival is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum IgM and 500mg/dL absolute increase from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).
Major Response Rate
时间窗: 4 years
Major Response Rate= Partial Response (\>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (\>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).
Very Good Partial Response and Complete Response Rate
时间窗: 4 years
This is the rate of VGPR and CR in patients on CaRD therapy. Very good partial responses are \>90% reduction in serum IgM from baseline. Complete response is defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.
次要结局
未报告次要终点
研究者
Steven P. Treon, MD, PhD
Principal Investigator
Dana-Farber Cancer Institute