A Phase 3 Multicenter, Randomized, Open-Label Study Evaluating the Safety and Efficacy of Etentamig (ABBV-383) Compared to Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone (Dara-CyBorD) in Subjects With Newly Diagnosed Amyloid Light Chain (AL) Amyloidosis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 370
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
Amyloid light chain (AL) amyloidosis is a rare disease caused by abnormal plasma cells producing misfolded light chain proteins that deposit in organs, leading to organ dysfunction and failure. The goal of this study is to evaluate the safety and efficacy of etentamig compared to daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in participants with newly diagnosed AL amyloidosis.
Etentamig is an investigational drug being developed for the treatment of newly diagnosed AL amyloidosis. This is an open-label study. The study consists of 2 parts: a Safety Run-in where participatns will receive etentamig, and a Randomized Portion with 2 treatment arms where participants will receive etentamig, or Dara-CyBorD. Approximately 370 participants will be enrolled in the study at approximately 130 sites worldwide.
Participants will receive injected etentamig, in the Safety Run-in. Participants will receive injected etentamig, or Dara-CyBorD per the local label, in the Randomized Portion of the study. The total study duration is approximately 96 months.
There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effects of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red-stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance.
- •Evidence of a monoclonal plasma cell proliferative disorder (serum or urine monoclonal protein, abnormal free light-chain ratio, or clonal plasma cells in the bone marrow).
- •Measurable disease of amyloid light chain (AL) amyloidosis as defined by difference in free light chains (dFLC) >= 50 mg/L
- •No history of treatment with anti-amyloidosis therapy.
- •Presence of an amyloid-related systemic syndrome with at least 1 organ impacted by AL amyloidosis according to International Myeloma Working Group (IMWG) diagnostic criteria.
- •Considered AL amyloidosis cardiac risk stage 1, 2, or 3a (or 3b [randomized portion only]).
- •Eastern Cooperative Oncology Group performance status <= 2.
排除标准
- •Known allergic reaction, significant sensitivity, or intolerance to constituents of the study treatments.
- •Active hepatitis B or hepatitis C infection.
- •History of other active malignancies within the past 3 years (with specified exceptions).
研究组 & 干预措施
Safety Run-in: Etentamig
Participants receive etentamig, as part of a 96 month study duration.
干预措施: Etentamig (Drug)
Randomized Portion: Etentamig
Participants will receive etentamig , as part of a 96 month study duration.
干预措施: Etentamig (Drug)
Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone
Participants will receive daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in accordance with the local approved label, as part of a 96 month study duration..
干预措施: Daratumumab (Drug)
Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone
Participants will receive daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in accordance with the local approved label, as part of a 96 month study duration..
干预措施: Cyclophosphamide (Drug)
Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone
Participants will receive daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in accordance with the local approved label, as part of a 96 month study duration..
干预措施: Bortezomib (Drug)
Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone
Participants will receive daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in accordance with the local approved label, as part of a 96 month study duration..
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Up to Approximately 96 Months
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. Safety and tolerability assessed through adverse events, laboratory tests, vital signs, physical examinations, and other safety assessments.
Randomized Portion: Complete Hematologic Response (HemeCR) Rate
时间窗: Up to Approximately 60 Months
HemeCR rate is defined as the proportion of subjects with the best overall response of hemeCR as determined by International Amyloidosis Consensus Criteria (IACC) and assessed by the independent review committee (IRC)
Randomized Portion: Major Organ Deterioration Progression-Free Survival (MOD-PFS)
时间窗: Up to Approximately 60 Months
MOD-PFS is defined as the time from the date of randomization to the date of MOD-PFS event or death from any cause, whichever occurs first. MOD-PFS includes: Development of hematologic progressive disease per consensus guidelines or high-risk difference in free light chain (dFLC) progression; Clinical manifestation of cardiac failure (defined as need for cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); Clinical manifestation of renal failure (defined as development of end-stage renal disease needing hemodialysis or renal transplant); Death. MOD-PFS will be assessed by an Independent Review Committee.
次要结局
- Safety Run-In: Major Organ Deterioration Progression-Free Survival (MOD-PFS)(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Overall Survival (OS)(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Percentage of Participants With Hematologic Very Good Partial Response (VGPR) or Better(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Cardiac Response Rate(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Renal Response Rate(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Liver Response Rate(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Next Treatment(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Complete Hematologic Response(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Duration of Complete Hematologic Response(Up to Approximately 60 Months)
- Randomized Portion: Time to Cardiac Response(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Renal Response(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Liver Response(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Duration of Cardiac Response(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Duration of Renal Progression(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Duration of Liver Response(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Cardiac Progression(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Renal Progression(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Liver Progression(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Maximum Serum Concentration (Cmax) of Etentamig(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Time to Maximum Serum Concentration (Tmax) of Etentamig(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Area Under the Concentration-Time Curve (AUC) of Etentamig(Up to Approximately 60 Months)
- Safety Run-In and Randomized Portion: Percentage of Participants With Anti-Drug Antibodies (ADA)(Up to Approximately 60 Months)
- Randomized Portion: Change from Baseline in Physical Functioning as Measured by 36-Item Short Form Health Survey Version 2 (SF-36 v2) Physical Component Summary Score(Up to Approximately 60 Months)
- Randomized Portion: Change from Baseline in Mental Functioning as Measured by SF-36 v2 Mental Component Summary Score(Up to Approximately 60 Months)
- Randomized Portion: Change from Baseline in Health-Related Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Fatigue Scale Score(Up to Approximately 60 Months)
- Randomized Portion: Change from Baseline in Fatigue as Measured by EORTC QLQ-C30 Fatigue Scale Score(Up to Approximately 60 Months)
- Randomized Portion: Change from Baseline in Disease Symptoms as Measured by Additional EORTC Questionnaire Symptom Scales/Items(Up to Approximately 60 Months)