An Open-label, Multicenter, Phase 2 Trial Investigating the Efficacy and Safety of Daratumumab in Subjects With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor and IMiD) or Are Double Refractory to a Proteasome Inhibitor and an IMiD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 124
- 主要终点
- Percentage of Participants With Overall Response
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are double refractory to a PI and an IMiD.
详细描述
This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.
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
- •Documented multiple myeloma according to protocol-defined criteria
- •Evidence of disease progression on the most recent prior treatment regimen based on International Myeloma Working Group criteria
- •Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
- •Laboratory values and electrocardiogram within protocol-defined parameters at screening
排除标准
- •Received daratumumab or other anti-CD38 therapies previously
- •Nonsecretory multiple myeloma
- •Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
- •Exhibiting clinical signs of meningeal involvement of multiple myeloma
- •Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
- •Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C
- •Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
研究组 & 干预措施
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
干预措施: Daratumumab 16 mg/kg (Part 1) (Drug)
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
干预措施: Daratumumab 8 mg/kg (Part 1) (Drug)
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
干预措施: Methylprednisolone (Drug)
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
干预措施: Acetaminophen (Drug)
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
干预措施: Diphenhydramine (Drug)
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
干预措施: Methylprednisolone (Drug)
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
干预措施: Acetaminophen (Drug)
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
干预措施: Diphenhydramine (Drug)
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
干预措施: Daratumumab (Part 2) (Drug)
结局指标
主要结局
Percentage of Participants With Overall Response
时间窗: Up to 14.4 Months
Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein level \< 100mg/24 hours; PR: \>= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
次要结局
- Time to Disease Progression(Up to 14.4 Months)
- Time to Response(Up to 14.4 Months)
- Overall Survival(Approximately up to 3 years)
- Progression Free Survival(Up to 14.4 Months)
- Duration of Response(Up to 14.4 Months)
- Percentage of Participants With Clinical Benefit(Up to 14.4 Months)