A Phase II Trial of Cyclophosphamide, Bortezomib and Dexamethasone (CYBOR-D) in Patients With Newly Diagnosed Active Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 63
- 试验地点
- 4
- 主要终点
- Number of Participants Who Achieved a Confirmed Responses Defined as a Complete Response (CR), Near CR or Very Good Partial Response (VGPR) After the First 4 Months of Treatment
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and dexamethasone work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide and dexamethasone together with bortezomib may kill more cancer cells.
PURPOSE: This phase II trial is studying giving cyclophosphamide and dexamethasone together with bortezomib to see how well it works in treating patients with newly diagnosed multiple myeloma.
详细描述
OBJECTIVES:
Primary
* To evaluate the response rate (complete response [CR], near CR [nCR], and very good partial response) in patients with newly diagnosed multiple myeloma treated with bortezomib in combination with cyclophosphamide and dexamethasone .
Secondary
- Determine the overall response rate (partial response, PR, or better) in these patients after 4, 8, and 12 courses of this regimen.
- Determine the duration of progression-free and overall survival of patients treated with this regimen.
- To evaluate the toxicity of this regimen in these patients.
- To evaluate the ability to successfully collect peripheral blood stem cells from these patients after 4 months of this regimen.
- To evaluate the CR or nCR rate in these patients after 8 and 12 courses of this regimen.
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
- •DISEASE CHARACTERISTICS:
- •Confirmed diagnosis of symptomatic multiple myeloma
- •Durie Salmon stage 2 or higher
- •Previously untreated multiple myeloma (including immunomodulatory drugs such as thalidomide) with the exception of bisphosphonates
- •Evaluable or measurable disease, as defined by at least one of the following:
- •Serum monoclonal protein ≥ 1 g/dL (measurable disease)
- •Urine monoclonal protein ≥ 200 mg/24 hours by protein electrophoresis (measurable disease)
- •Serum-free light chains (FLC) ≥ 10 mg/dL, kappa or lambda, accompanied by an abnormal kappa/lambda ratio
- •Serum FLC's should only be used for patients without measurable serum or urine m-spike
- •- Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
- •* Patients diagnosed with smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible
- •PATIENT CHARACTERISTICS:
- •Inclusion criteria:
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2
- •- ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator
- •Total bilirubin normal OR direct bilirubin ≤ 2.0 mg/dL
- •Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
- •AST ≤ 3 times ULN
- •Creatinine ≤ 3.5 mg/dL
- •Absolute neutrophil count ≥ 1,000/mm³ without transfusion or growth factor
- •Platelet count ≥ 100,000/mm³ without transfusion or growth factor
- •Willingness and the physical and mental capability to provide written informed consent
- •Willingness to return to Mayo Clinic Arizona/Princess Margaret Hospital for follow-up
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
排除标准
- •Peripheral sensory neuropathy ≥ grade 2 as defined by National Cancer Institute (NCI) Common Terminology for Common Adverse Events (CTCAE) version 3.0
- •Known hypersensitivity to compounds containing boron or mannitol
- •Active uncontrolled infection
- •Severe cardiac comorbidity including but not limited to:
- •New York Heart Association class III or IV heart failure
- •History of myocardial infarction within the past 6 months
- •Uncontrolled angina or electrocardiographic (ECG) evidence of acute ischemia
- •Severe uncontrolled ventricular arrhythmias or ECG evidence of active conduction system abnormalities
- •Cardiac amyloidosis with hypotension (i.e., systolic blood pressure < 100 mm Hg)
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent study compliance or completion of study treatment
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Prior high-dose corticosteroid therapy for 12 days or less is permitted for emergent complications from newly diagnosed multiple myeloma
- •More than 14 days since prior investigational agents
- •No concurrent steroids or any other anticancer agents or treatments
- •- Patients may receive the equivalent of up to 20 mg prednisone per day for concurrent illness or adrenal replacement therapy
- •Concurrent palliative radiotherapy for bony pain or fracture is allowed
结局指标
主要结局
Number of Participants Who Achieved a Confirmed Responses Defined as a Complete Response (CR), Near CR or Very Good Partial Response (VGPR) After the First 4 Months of Treatment
时间窗: After 4 months of treatment
Response that was confirmed on 2 consecutive evaluations during the first 4 months of treatment. Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and \<5% plasma cells in bone marrow. near Complete Response (nCR): Patients who meet all criteria for CR except a positive immunofixation will be classified as nCR. Very Good Partial Response(VGPR): \>=90% reduction in serum M-component; Urine M-Component \<100mg per 24hours; \<=5% plasma cells in bone marrow.
次要结局
- Duration of Response(Duration of study (up to 12 cycles))
- Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 12 Cycles(After 12 cycles of treatment)
- Number of Participants Who Responded to Treatment (CR, nCR, VGPR or PR) After 8 Cycles(After 8 cycles of treatment)
- Participants Who Successfully Completed Collection of Peripheral Blood Stem Cells for Transplant(After 4 cycles of treatment)
- Progression Free Survival (PFS)(up to 5 years)
- Overall Survival (OS)(From date of registration until death (up to 5 years))
- Number of Participants Who Responded to Treatment (Complete Response,CR; Near Complete Response, nCR; Very Good Partial Response, VGPR; or Partial Response, PR) After 4 Cycles(4 cycles)
- Number of Participants With Severe Adverse Events(Every cycle during treatment (up to 12 cycles))