jRCT2031210017进行中（未招募）不适用
A Phase 3 randomized, open label, multicenter study of isatuximab (SAR650984) in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- Sanofi K.K.
- 入组人数
- 300
- 主要终点
- Plasma concentration of isatuximab: Cmax - Safety Run-in Part
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized Controlled Trial
- 干预模型
- Parallel Assignment
- 主要目的
- Treatment Purpose
- 盲法
- Open(masking Not Used)
入排标准
- 年龄范围
- 18age old over 至 No limit（—）
- 性别
- All
入选标准
- •Participants who are diagnosed within 5 years with SMM (per International Myeloma Working Group [IMWG] criteria), defined as serum M-protein >=30 g/L or urinary M-protein >=500 mg per 24 hour or both, and/or clonal bone marrow plasma cells (BMPCs) 10% to <60%, and absence of myeloma defining events or other related conditions and with high-risk SMM
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or 2
- •Capable of giving voluntary written informed consent
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement):
- •a) Increased calcium levels: Corrected serum calcium >1 mg/dL above the ULN or >11 mg/dL
- •b) Renal insufficiency: Determined by glomerular filtration rate (GFR) <40 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] Formula) or serum creatinine >2 mg/dL
- •c) Anemia (hemoglobin 2 g/dL below lower limit of normal or <10 g/dL or both). Transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
- •d) >=1 bone lytic lesion
- •e) BMPCs >=60%
- •f) Serum involved/uninvolved FLC ratio >=100 and an involved FLC >= 100mg/L
- •g) Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 bone focal lesion (>=5 mm in diameter by MRI)
- •Primary systemic amyloid light-chain (AL) amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, soft-tissue plasmacytoma, and symptomatic myeloma
- •Uncontrolled infection within 28 days prior to randomization in Phase 3 or first study intervention administration in safety run-in
- •Clinically significant cardiac or vascular disease within 3 months prior to randomization, e.g. Myocardial Infarction; Unstable Angina; Coronary (e.g. Coronary Artery Bypass Graft, Percutaneous Coronary Intervention) or peripheral artery revascularization, Left Ventricular Ejection Fraction <40%, Heart Failure NYHA III-IV, Stroke, Transient Ischemic Attack, Pulmonary Embolism, other thromboembolic event, cardiac arrhythmia (Grade 3 or higher by NCI-CTCAE Version 5.0)
- •Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A (defined as positive hepatitis A antigen or positive IgM). HIV serology at screening will be tested for German participants and any other country where required as per local regulations and serology hepatitis B and C at screening will be tested for all participants.
- •Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA
- •- Patient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period.
- •- Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met.
- •Active HCV infection: positive HCV RNA and negative anti-HCV
- •- Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.
- •- Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible
- •Malabsorption syndrome or any condition that can significantly impact the absorption of lenalidomide
- •Any of the following within 3 months prior to randomization (or first study intervention administration in safety run-in cohort): treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis.
- •Received treatment (eg surgery, radiotherapy, medication) for a malignancy within 3 years of randomization (or first study intervention administration in safety run-in cohort)
- •Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory imid drugs, or Proteasome inhibitors); concurrent use of bisphosphonates or receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab is not permitted; however, prior bisphosphonates or once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is permitted
- •Ongoing treatment with corticosteroids with a dose >10 mg prednisone or equivalent per day at the time of randomization (or first study intervention administration in safety run-in cohort)
- •Women of childbearing potential or male participant with women of childbearing potential who do not agree to use a highly effective method of birth control
- •Vaccination with a live vaccine 4 weeks before the start of the study drug. Seasonal flu vaccines that do not contain live virus are permitted
- •Note: Other Inclusion/Exclusion criteria may apply.
结局指标
主要结局
Plasma concentration of isatuximab: Cmax - Safety Run-in Part
时间窗: After first infusion in Cycle 1 in safety run-in part. 1 cycle = 28 days
Maximum concentration observed after the first infusion (Cmax)
Receptor density/receptor occupancy Safety Run-in Part
时间窗: Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Change in CD38 receptor occupancy from baseline
Progression-free survival (PFS) Randomized Phase 3
时间窗: Up to approximately 114 months
Time from randomization to MM (SLiM CRAB criteria) or other related conditions based on independent review committee assessment according to 2014 International Myeloma Working Group (IMWG) criteria or death from any cause, whichever happens first
Safety assessment: adverse events (AEs) - Safety Run-in Part
时间窗: Up to approximately 63 months
Number of participants with AEs
次要结局
- Overall response rate (ORR) - Safety Run-in Part and Randomized Phase 3(Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively)
- Duration of response (DOR) - Safety Run-in Part and Randomized Phase 3(Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively)
- Minimal residual disease (MRD) negativity - Safety Run-in Part and Randomized Phase 3(Up to approximately 65 months)
- Time to diagnostic (SLiM CRAB) progression or death - Safety Run-in Part and Randomized Phase 3(Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively)
- Time to first-line treatment for multiple myeloma (MM) - Safety Run-in Part and Randomized Phase 3(Up to approximately 63 and 114 months for Safety Run-in Part and Randomized Phase 3, respectively)
- Immunogenicity: Incidence of anti-drug antibodies (ADA) - Safety Run-in Part(Up to approximately 27 months)
- Sustained MRD negativity - Randomized Phase 3(Up to approximately 65 months)
- Second PFS (PFS2) Randomized Phase 3(Up to approximately 144 months)
- Overall survivall - Randomized Phase 3(Up to approximately 144 months)
- Complete response rate - Randomized Phase 3(Up to approximately 114 months)
- Safety assessment: adverse events (AEs) - Randomized Phase 3(Up to approximately 144 months)
- Plasma concentration of isatuximab - Randomized Phase 3(At predose of Cycle 2 Day 1 and Cycle 6 Day 1)
- European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 - Randomized Phase 3(Baseline to follow-up (up to approximately 7 years))
- EORTC QLQ-MY20 - Randomized Phase 3(Baseline to follow-up (up to approximately 7 years))
- EQ-5D-5L - Randomized Phase 3(Baseline to follow-up (up to approximately 7 years))
- Randomized Phase 3: HRUPQ - Randomized Phase 3(Baseline to follow-up (up to approximately 7 years))
- Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2) - Randomized Phase 3(End of treatment (up to approximately 5 years))
研究者
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