A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 480
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
- 干预模型
- Randomized No Masking
- 主要目的
- Treatment Purpose
入排标准
- 年龄范围
- 20age old over 至 No limit（—）
- 性别
- All
入选标准
- •Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen
- •Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course
- •of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy
- •Documented multiple myeloma as defined by the criteria below:
- •Multiple myeloma diagnosis according to the IMWG diagnostic criteria
- •Measurable disease at Screening as defined by any of the following:
- •a) Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
- •b) Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- •Meet the clinical laboratory criteria as specified in the protocol
- •Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization
排除标准
- •Received daratumumab or other anti-CD38 therapies previously
- •Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer,before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days before treatment
- •Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing)
- •Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)
- •History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years.
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: At 6 months after 480 participants have been randomized (approximately 2years)
The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 mg/24hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the Mprotein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place ofM+H30-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Maximum Trough Concentration (Ctrough) of Daratumumab
时间窗: Cycle 3 (each cycle 28 days) Day 1
Maximum Ctrough is defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Percentage of participants With Infusion-Related Reactions (IRR)
时间窗: At 6 months after 480 participants have been randomized (approximately 2years)
The Percentage of Participants with infusion reactions will be reported.
Progression-Free Survival (PFS)
时间窗: At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized(approximately 3 years)
PFS is defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. According to IMWG criteria: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow 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.
Very Good Partial Response (VGPR) or Better Rate
时间窗: At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years)
The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according IMWG criteria during or after the study treatment. IMWG criteria for VGPR:Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram(mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5%plasma cellS (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), munofluorescencea or 2- to 4 color flow cytometry
次要结局
- Complete Response (Including sCR) or Better Rate(At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years))
- Time to Next Treatment(At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized(approximately 3 years))
- Overall Survival (OS)(At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years))
- Patient-Reported Satisfaction With Therapy(At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years))
- Duration of Response(At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years))
- Time to response(At 6 months after 480 participants have been randomized (approximately 2years) and 24 months after the last participant randomized (approximately 3 years))