Phase II, Single-arm Trial of Carfilzomib, Lenalidomide, and Dexamethasone Re-induction Followed by the 2nd ASCT in Multiple Myeloma Patients Relapsed After the 1st ASCT
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- 2-year progression free survival rate
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of salvage treatment with carfilzomib/lenalidomide/dexamethasone (KRD) followed by 2nd autologous stem cell transplantation (ASCT) and lenalidomide maintenance in patients with relapsed myeloma after 1st ASCT.
详细描述
This is a single-arm phase II study to assess the efficacy and safety of KRD followed by 2nd ASCT - lenalidomide maintenance for 18 months in patients with relapsed multiple myeloma after 1st ASCT who are 70 years of age or younger. A total of 58 participants will be recruited. As a re-induction therapy 6 cycles of KRD (K, 27mg/m2, D1,2,8,9,15,16; R, 25 mg, D1-21; D, 40mg weekly, every 28 days) will be administered. If a patient achieves at least partial response, 2nd ASCT + lenalidomide 10mg for 18 months will be proceeded. Study will be continued until disease progression, unacceptable toxicity, or completion of pre-planned schedule. Response will be assessed using the International Myeloma Working Group(IMWG) response criteria and the safety profiles will be described using the NCI-CTCAE v5.0. Participants who discontinue therapy will be followed every 3 months for 3 years if they are on subsequent treatment, disease-free or dead.
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
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Progressive disease after 1st ASCT
- •Duration of response after 1st ASCT > 12 months
- •Measurable disease (+)
- •Serum M-protein ≥ 1 g/dL
- •Urine M-protein ≥ 200 mg/24 hr
- •Serum Free Light Chain(FLC) assay: involved FLC level ≥10 mg/dL (serum Free Light Chain ratio is abnormal)
- •Adequate organ function for induction & ASCT
- •Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
- •Platelets ≥ 50 x 109/L (≥ 30 x 109/L if myeloma involvement is > 50% in the bone marrow)
- •Hemoglobin ≥ 8.0 g/dL
- •Creatinine clearance ≥ 30 mL/minute
- •Serum Bilirubin ≤ 1.5 x upper limit of normal
- •Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) ≤ 3 x upper limit of normal
- •Eastern Cooperative Oncology Group performance scale 0~2
- •Survival expectancy > 3 months
- •Adequately controlled hepatitis B(HBV) & hepatitis C(HCV)
- •Written informed consent
- •Optimal contraceptions
排除标准
- •Prior refractoriness or intolerance to carfilzomib
- •Prior refractoriness or intolerance to lenalidomide/dexamethasone
- •Any treatment after progressive disease after 1st ASCT. High-dose dexamethasone or palliative radiation is permitted.
- •Waldenstroem's macroglobulinemia, POEMS syndrome, or plasma cell leukemia
- •Pregnant or nursing lactating women
- •Myocardial infarct within 6 months, heart failure of New York Heart Association(NYHA) Class III~IV, uncontrolled ventricular arrhythmia, severe coronary arterial obstructive disease
- •Uncontrolled hypertension (Defined as an average systolic blood pressure >= 160 mmHg or diastolic >= 100 mmHg) or diabetes
- •Grade 3~4 neuropathy
- •HIV infection
- •Severe or uncontrolled medical conditions, laboratory abnormalities, or psychiatric disorders that may preclude the participation of the study by the physician's discretion
- •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
- •Diagnosis of other malignant disease other than myeloma within 5 year. Exceptions are properly treated non-melanomatous skin cancers, cervical intraepithelial neoplasia, prostate cancer that do not require treatment, or properly excised well-differentiated thyroid cancers
研究组 & 干预措施
Single arm of Lenalidomide maintenance
[KRd #1~6, Every 4 weeks] D1, 2, 8, 9, 15,16 Carfilzomib 20mg/m2 + 5% dextrose in water 50 mL over 10 mins (From Cycle1Day8 27mg/m2) D1 - 21 Lenalidomide 25mg P.O. D1, 8, 15, 22 Dexamethasone 40mg IV or PO
[Autologous stem cell transplantation phase]
[Lenalidomide maintenance phase, Every 4 weeks] D1-28 Lenalidomide 10 mg
干预措施: Lenalidomide maintenance (Drug)
结局指标
主要结局
2-year progression free survival rate
时间窗: 2-years after the written consent
percentage of patients who are disease free or alive at 2-years
次要结局
- Time to response(assessed for approximately 3 years after administration)
- Complete response rate after KRd #6(total 6 cycles (each cycle is 28 days) of induction therapy)
- Complete response rate after ASCT(at the time of 2nd ASCT (within 60 days after ASCT))
- Overall response rate(assessed for approximately 3 years after administration)
- Duration of response(assessed for approximately 3 years after administration)
- Overall survival(assessed for approximately 3 years after administration)
- Safety of KRd induction therapy, 2nd ASCT, and lenalidomide maintenance therapy(assessed for approximately 2 years during administration)
- Rate of the successful stem cell harvest(total 6 cycles (each cycle is 28 days) of induction therapy)
研究者
Kihyun Kim
Professor
Samsung Medical Center