A Multicenter Open Label Phase 2 Study of Carfilzomib Weekly Plus Melphalan and Prednisone in Untreated Symptomatic Elderly Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 66
- 主要终点
- Dose Maximum Tolerate of Carfilzomib Weekly
研究概览
简要总结
IFM 2012-03 protocol is a Phase 2 multicenter nonrandomized open in elderly patients with multiple myeloma at diagnosis. Study primary objectives are in the first step to determine Maximum tolerated dose (MTD) of Carfilzomib Weekly based on definition of Dose-limiting toxicities (DLTs) and in the second step to expanded cohort, to determine the VGPR (Very Good Partial Response) + CR (Complete Response) rate of Carfilzomib Weekly at the MTD in combination with Melphalan Prednisone at the end of the 9 induction cycles.
详细描述
Overall design. This study is a Multicenter, Open-label, Phase 2 study of Carfilzomib Weekly +MP in Untreated Elderly MM. Eligible patients must have a symptomatic, untreated MM with a measurable disease. There is a dose escalation part in the study as the MTD remained to be determined for carfilzomib weekly given for 4 infusions (day 1, 8, 15, 22) on a 35-days cycle.
This study will thus comprise 2 parts. Step 1. To determine MTD of Carfilzomib Weekly based on definition of DLTs - (N=6 patients per cohort, maximum 5 cohorts of carfilzomib weekly +MP) The patients will be included into three cohorts at 36 mg/m², 45 mg/m², 56 mg/m² and 70mg/m² of Carfilzomib Weekly given for 4 infusions (day 1, 8, 15, 22) +MP given on days 1 to 4 of a 35-days cycle. Carfilzomib will be administered at a dose of 36mg/m² for the first cohort where the 20 mg/m² dose is administered on Day 1 of Cycle 1 only and then 36 mg/m² for all subsequent doses.
If dose-limiting toxicities (DLTs) occur in fewer or equal than 2 of these patients, the next cohort of 6 patients (cohort 2) will be opened and patients will receive a dose of 20/45 mg/m². If DLTs occur in fewer or equal than 2 of the patients in cohort 2, the third cohort of 6 patients will receive a dose of 20/56 mg/m² where the 20 mg/m² dose is administered on Day 1 of Cycle 1 only and then 56 mg/m² for all subsequent doses. If DLTs occur in fewer or equal than 2 of the patients in cohort 3, the fourth and five cohort of 6 patients will receive a dose of 20/70 mg/m² where the 20 mg/m² dose is administered on Day 1 of Cycle 1 only and then 70 mg/m² for all subsequent doses.
If at any time during cycle 1 of a dose cohort, > 2 subjects experience a drug-related DLT, the MTD will have been exceeded, additional enrolment within the cohort will cease, and dose escalation will stop. The MTD will be defined as the dose level below which DLT is observed in > 33% (i.e. > 2 of 6) subjects in a cohort.
The following are defined as DLTs:
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •able to understand and voluntarily sign an informed consent form
- •able to adhere to the study visit schedule and other protocol requirements.
- •age ≥ 65 years.
- •life expectancy > 6 months.Patients must have Symptomatic Measurable previously Untreated MM
- •have measurable disease as defined by the following: quantifiable monoclonal M-component value in the serum and/or urine
- •eastern Cooperative Oncology Group performance status score ≤2
- •dequate bone marrow function, documented within 72 hours and without transfusion 5 days prior to the first intake of investigational product no growth factor support Adequate organ function
- •subjects affiliated with an appropriate social security system.
- •male subjects must:Understand the potential teratogenic,and genotoxic risk of Melphalan if engaged in sexual activity with a pregnant female or a female of childbearing potential.
- •understand the potential genotoxic risk of Carfilzomib if engaged in sexual activity with a pregnant female or a female of childbearing potential.
- •practice complete abstinence or understand the need and agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential throughout the entire duration of study treatment, during dose interruptions and until at least 3 months after the end of treatment discontinuation of CMP, even if he has undergone a successful vasectomy.
- •if pregnancy or a positive pregnancy test does occur in the partner of a male study patient during study participation, the investigator must be notified immediately.
- •agree not to donate semen or sperm during study drug therapy and until at least 3 months after the end of treatment discontinuation of CMP.
排除标准
- •any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
- •known positive for HIV or active infectious hepatitis, type B or C.
- •patient with terminal renal failure that require dialysis and clearance creatinine < 30 ml/min.
- •prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for ≥ 5 years.
- •prior local irradiation within two weeks before first dose
- •evidence of central nervous system (CNS) involvement.
- •unable to take corticotherapy at study entry
- •any ongoing adverse event or medical history > grade 2 severity
- •persons protected by a legal regime (guardianship, trusteeship).Alkeran's (Melphalan) contraindication: Hypersensitivity to Melphalan or to any other constituents.
- •patients with heart failure class 3 and 4 according to the NYHA criteria, or patients with past history of myocardial infarction within the last 6 months or no controlled cardiac conduction abnormalities.
- •patients with a left ventricular ejection fraction under or equal to 45 % (LVEF ≤ 45%)
研究组 & 干预措施
Carfilzomib weekly+Melphalan+Prednisone
one arm, two steps and two parts.In the first step of the study: 5 cohorts of 6 patients with Carfilzomib weekly administrated at different dose regimen will be opened one after the other to determine Maximum tolerated dose of Carfilzomib based on definition of Dose-limiting toxicities.In the second step of the study:expanded Cohort, 50 patients received Carfilzomib at the MTD. In Part 1. Induction.Nine 5 weeks cycles of weekly CMP are plannedCarfilzomib. 36, 45, 56 or 70 mg/m² on days 1, 8, 15, 22 IV route . Patients will start the first cycle day 1 with 20mg/m². In combination with oral Melphalan 0.25mg/kg/j and oral prednisone 60mg/m², both on days 1 to 4.Part 2. Maintenance.Carfilzomib. 36 mg/m² weekly, every two weeks IV route for 1 year.
干预措施: Carfilzomib (Drug)
结局指标
主要结局
Dose Maximum Tolerate of Carfilzomib Weekly
时间窗: 35 days
If dose-limiting toxicities occur in fewer than 3 of these patients per cohort, the next cohort of 6 patients (cohort 2,3 and 4) will be open. If at any time during cycle 1 of a dose cohort, \> 2 subjects experience a drug-related dose-limiting toxicities, the Maximum Tolerate Dosing will have been exceeded, additional enrolment within the cohort will cease, and dose escalation will stop. The Maximum Tolerate Dosing will be defined as the dose level below which dose-limiting toxicities is observed in \>33% subjects in a cohort.
次要结局
- number of patients who reach Very Good Partial Response and Complete(315 days)