A Prospective, Multi-center, Open-label, Cohort Study to Compare Daratumumab-Lenalidomide-Dexamethasone (DRd) With Modified Bortezomib-Lenalidomide-Dexamethasone (VRd-lite) in Elderly Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 6
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The purpose of the study is to compare the efficacy and safety of daratumumab, lenalidomide and dexamethasone (DRd) to that of modified bortezomib, lenalidomide and dexamethasone (VRd-lite), in terms of progression-free survival and minimal residual disease negativity rate in elderly participants with newly diagnosed multiple myeloma.
详细描述
This is a prospective, open-label, multicentered cohort study. This study will evaluate elderly participants with newly diagnosed multiple myeloma (MM) for whom hematopoietic stem cell transplant is not planned as initial therapy. All the eligible participants can be free to choose to receive either daratumumab lenalidomide and dexamethasone (DRd) or modified bortezomib lenalidomide and dexamethasone (VRd-lite). Daratumumab (16 milligram per kilogram [mg/kg]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (Cycle 7 to 8). Bortezomib will be administered subcutaneously 1.3 mg/m^2 weekly of each 28-day cycle for Cycles 1-8. Lenalidomide will be administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and dexamethasone will be administered at a dose of 20 mg twice a week for both treatment arms. Participants in both treatment arms will continue at least lenalidomide maintenance until disease progression or unacceptable toxicity.The primary endpoint will be progression-free survival (PFS) and percentage of participants with Negative Minimal Residual Disease (MRD). Participant safety will be assessed throughout the study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Age ≥ 65 years old
- •Newly diagnosed Multiple myeloma patients with measurable disease. Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria：Monoclonal plasma cells in the bone marrow greater than or equal to (>=)10 percentage (%) or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or SLiM. CRAB criteria: Hypercalcemia: serum calcium greater than (>) 0.25 millimoles per liter (mmol/L) (>1 milligram per deciliter [mg/dL]) higher than upper limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL); Renal insufficiency: creatinine clearance less than (<) 40 milliliter per minute (mL/min) or serum creatinine >177 micro millimoles per liter (umol/L) (>2 mg/dL); Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL; Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT. SLiM: Clonal bone marrow plasma cell percentage >=60%; Involved: uninvolved serum free light chain (FLC) ratio >=100; >1 focal lesion on magnetic resonance imaging (MRI) studies.
- •Measurable disease: Immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein [M-protein] level >= 0.5 gram/deciliter [g/dL] or urine M-protein level >= 200 milligram[mg]/24 hours[hrs]); OR IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level >= 0.2 g/dL or urine M-protein level >= 200 mg/24 hrs); OR Light chain multiple myeloma (serum immunoglobulin free light chain >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
- •Expected survival more than 3 months
- •No active infectious disease
- •Be able to understand the characteristics of the disease, voluntarily join this study protocol for treatment and follow-up
- •Have signed informed consent. Informed consent was obtained from the patients themselves or their immediate family members.
排除标准
- •Patients with active hepatitis B (HBV), hepatitis C (HCV), and other acquired, congenital immunodeficiency diseases.
- •Peripheral neuropathy or neuropathic pain(except extramedullary disease compression) Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version
- •Plasma cell leukemia, non-bone-related extramedullary lesions
- •Severe thrombotic events before treatment
- •The presence of grade 2 or higher peripheral neuropathy before treatment
- •Liver dysfunction (alanine aminotransferase and aspartate aminotransferase ≥ 2.5 times the upper limit of normal value)
- •Total bilirubin ≥ 1.5 times the upper limit of normal value
- •Major surgery within 30 days before enrollment
- •Epilepsy, dementia and other mental abnormalities requiring drug treatment and cannot understand or follow the study protocol
- •According to the protocol or the investigator's judgment, the patient has a serious physical or mental illness that may interfere with the participation in this clinical study
- •Drug abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of the study results
- •Patients who are receiving other experimental drug treatment
- •Lactating or pregnant women
- •The investigator believes that the participant is not suitable for enrollment
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From enrollment to either disease progression or death whichever occurs first (approximately 5 years, or 8 years if the adaptive approach is decided at the interim)
PFS is defined as the duration from date of enrollment to either progression disease(PD) or death, whichever comes first. International Myeloma Working Group (IMWG) criteria for PD: Increase of 25 percentage (%) from lowest response value in any one of following: Serum M-component (absolute increase must be \>= 0.5 g/dL) Urine M-component (absolute increase must be \>=200 mg/24 hours), participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain(FLC) levels (absolute increase must be \>10 mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell(PC)% (absolute percentage must be \>=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
MRD Negative Rate
时间窗: First time reached VGPR, then12,18,24 Months and every 6 months
Percentage of participants who have achieved MRD negative status will be assessed. MRD negativity will be evaluated as a potential surrogate for PFS and overall survival (OS) in multiple myeloma treatment.
次要结局
- Duration of Response(DOR)(From initial documentation of response to the date of PD until approximately 5 years)
- Very Good Partial Response (VGPR) or Better Rate(Approximately 5 years)
- Overall Response Rate(Up to the end of the study (approximately 5 years))
- Overall Survival (OS)(From enrollment until the participant's death from any cause (up to approximately 5 years, or 8 years if the adaptive approach is decided at the interim))
- Complete Response (CR) or Better Rate(Approximately 5 years)