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
- 522
- 试验地点
- 146
- 主要终点
- Maximum Trough Concentration (Ctrough) of Daratumumab
研究概览
简要总结
The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).
详细描述
The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
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:
- •Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
- •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
研究组 & 干预措施
Dara SC
Participants will receive a fixed dose of daratumumab as 1800 milligram (mg) subcutaneously (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.
干预措施: Dara SC (Drug)
Dara IV
Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.
干预措施: Dara SC (Drug)
Dara IV
Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.
干预措施: Dara IV (Drug)
结局指标
主要结局
Maximum Trough Concentration (Ctrough) of Daratumumab
时间窗: Predose on Cycle 3 Day 1 (each cycle of 28 days)
Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Overall Response Rate (ORR)
时间窗: Up to 1 year 8 months
ORR was defined as the percentage of participants who achieved 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 milligrams (mg)/24 hours, If the serum and urine M-proteins are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels were required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-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 was also required.
次要结局
- Progression Free Survival (PFS)(Up to 3 years)
- Percentage of Participants With Complete Response (Including sCR) or Better(Up to 3 years)
- Time to Next Therapy(Up to 3 years)
- Overall Survival (OS)(Up to 3 years)
- Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)(Up to 3 years)
- Time to Very Good Partial Response (VGPR) or Better(Up to 3 years)
- Percentage of Participants With Very Good Partial Response (VGPR) or Better(Up to 3 years)
- Duration of Response(Up to 3 years)
- Time to Partial Response (PR) or Better(Up to 3 years)
- Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)(Cycle 1 (Days 8,15 and 22), Cycle 2 (Days 1,8,15 and 22), Cycle 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 and 22 (Day 1))
- Time to Complete Response (CR) or Better(Up to 3 years)