A MULTICENTER, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 13
- 主要终点
- Toxicity: Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0)
研究概览
简要总结
The purpose of this study is to determine whether the association of Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) as induction treatment is safe and provides benefits in patients with newly diagnosed Multiple Myeloma (MM).
详细描述
This protocol is a phase II multicenter, international, non-comparative, open label study designed to jointly assess the safety and the efficacy of the association Carfilzomib with Cyclophosphamide and Dexamethasone (CCd) as induction treatment and Carfilzomib alone as maintenance in newly diagnosed MM patients.
Patients will be evaluated at scheduled visits in up to 4 study periods: pre-treatment, treatment, maintenance and long-term follow-up.
The pre-treatment period includes screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above.
The treatment period includes administration of Carfilzomib, Cyclophosphamide and Dexamethasone for 9 4-week courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled Carfilzomib administration. The response will be assessed after each 4-week cycle.
The maintenance period includes carfilzomib alone on days 1, 2, 15, 16 at 36mg/m2. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator. It will be initiated at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years.
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
- •Patient is of a legally consenting age as defined by local regulations.
- •Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell transplantation.
- •Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
- •Patient has given 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 patient at any time without prejudice to their future medical care.
- •Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- •Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
- •Patient is a newly diagnosed MM patient.
- •Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results.
- •- Patient has a Karnofsky performance status ≥60%.
- •Patient has a life-expectancy >3 months.
- •Patient has the following laboratory values within 14 days before Baseline (day
- •1 of the Cycle 1, before study drug administration):
- •Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration).
- •Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors.
- •Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)
- •Alanine transaminase (ALT): ≤ 3 x the ULN.
- •Total bilirubin: ≤ 2 x the ULN.
- •Calculated or measured creatinine clearance: ≥ 15 mL/minute
排除标准
- •- Patients with non-secretory MM, unless serum free light chains are present and the ratio is abnormal.
- •Pregnant or lactating females
- •Patient has active infectious hepatitis type B or C or HIV.
- •Patients with myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
- •Peripheral neuropathy > CTCAE grade 2 and ≥ grade 2 painful peripheral neuropathy (with the difference being in the exclusion of patients with Grade 2 painful PN).
- •Known history of allergy to Capsidol (a cyclodextrin derivative used to solubilize carfilzomib)
- •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.
- •Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to baseline;
- •Patient has any other clinically significant illness that would, in the investigator's opinion, increase the patient's risk for toxicity.
- •Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix or breast, or localized prostate cancer of Gleason score <7 with a stable PSA)
研究组 & 干预措施
Carfilzomib Cyclophosphamide Dexamethasone
The treatment period includes administration of Carfilzomib Cyclophosphamide Dexamethasone for 9 courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled carfilzomib administration. The response will be assessed after each cycle.
干预措施: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE (Drug)
结局指标
主要结局
Toxicity: Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0)
时间窗: 4 years
Toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity excluding anemia, (grade 4 neutropenia must last longer than 3 days and grade 4 thrombocytopenia must last longer than 7 days in order to be considered a toxicity) with the exception of (grade 4 neutropenia \> 3 days , or grade 4 thrombocytopenia \>7 days duration) or grade 3 non-hematologic drug-related toxicity.
Efficacy will be assessed by considering partial response (PR) following the proposed regimen. Assessment of Partial Response rate will be performed at the end of third cycle according to the criteria of the International Myeloma Working Group.
时间窗: 4 years
次要结局
- Progression Free Survival(4 years)
- β2-microglobulin as prognostic factors(4 years)
- peripheral neuropathy(4 years)
- C reactive protein as prognostic factors(4 years)
- cytogenetics as prognostic factors(4 years)
- Response rate(4 years)
- Duration of Progression Free Survival(4 years)
- Time to progression (TTP)(4 years)
- Duration of Response (DOR)(4 years)
- Duration of Overall Survival(4 years)
- Time to next therapy(4 years)
- Progressio Free Survival(4 years)
- microRNA(4 years)
- gene expression profile(4 years)
- Overall Survival(4 years)