A Phase III Randomized, Controlled, Multicenter, Open-label Study of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients With Relapsed or Refractory Multiple Myeloma (RRMM)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 154
- 试验地点
- 33
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a Phase III Randomized, Controlled, Multicenter, Open-label Study of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM).
详细描述
This is a Phase III Randomized, Controlled, Multicenter, Open-label Study of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM). About 150 subjects are planned to be enrolled in this study, and be randomized into two treatment Arms in a 2:1 allocation (SVd Arm or Vd Arm).
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
- •Understand and voluntarily sign an informed consent form (ICF).
- •Age ≥ 18 years.
- •Confirmed MM with measurable disease per IMWG guidelines, and meet at least 1 of the following:
- •Serum M-protein ≥ 0.5 g/dL (> 5 g/L) by serum protein electrophoresis (SPEP) or for immunoglobulin IgA, IgD myeloma, replaced by quantitative serum IgA, IgD levels; or
- •Urinary M-protein level ≥ 200 mg/24 hours; or
- •Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal (Normal FLC ratio: 0.26 to 1.65).
- •Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens. Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 anti-MM regimen.
- •Valid evidence of progressive MM (based on the Investigator's determination according to the IMWG response criteria) on or after their last regimen.
- •Must have an ECOG Status score of 0, 1, or
- •Renal function should meet the following criteria: creatinine clearance [CrCl] rates ≥ 20 mL/min (Calculated using the formula of Cockroft and Gault).
- •Resolution of any clinically significant non-hematological toxicities (If any) from previous treatments to Grade ≤1 or baseline by C1D
- •Subject with chronic, stable Grade 2 non hematological toxicities may be included following approval from the Medical Monitor.
- •Female subjects of childbearing potential must have a negative serum pregnancy test at Screening. Female subjects of childbearing potential and fertile male subjects must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
排除标准
- •Prior exposure to SINE compounds (Including ATG-010), or suspected allergy to SINE or similar drugs.
- •Active plasma cell leukemia.
- •Documented systemic light chain amyloidosis.
- •MM involving the central nervous system.
- •POEMS syndrome (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).
- •Spinal cord compression related to MM.
- •Greater than Grade 2 peripheral neuropathy or Grade ≥ 2 peripheral neuropathy with pain at baseline, regardless of whether the subject is currently receiving medication.
- •Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
- •Active graft versus host disease (After allogeneic stem cell transplantation) at screening.
- •Uncontrolled active infections requiring intravenous antibiotics, antivirals, or antifungal therapy in 2 weeks prior to C1D
- •Major surgery within 4 weeks prior to C1D
- •Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
- •Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus deoxyribonucleic acid (HBV-DNA).
- •Pregnant or lactating women.
- •Life expectancy of < 4 months.
- •Any active gastrointestinal dysfunction interfering with the subject's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
- •Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
- •Contraindication to any of the required concomitant drugs or supportive treatments.
- •Any diseases or complications which may interfere with the study procedures.
- •Subject unwilling or unable to comply with the protocol.
研究组 & 干预措施
SVd (Selinexor+Bortezomib+dexamethasone)
Enrolled patients will be treated with ATG-010( 100 mg/QW, oral ) with Bortezomib( 1.3 mg/QW, hypodermic injection ) +dexamethasone ( 20 mg/QW, oral ) about 13.5cycles.
干预措施: SVd (Selinexor+Bortezomib+dexamethasone) (Combination Product)
Vd(Bortezomib+dexamethasone)
Enrolled patients will be treated with Bortezomib( 1.3 mg/QW, hypodermic injection ) +dexamethasone ( 20 mg/QW, oral ) about 13.5 cycles.
干预措施: Vd (Bortezomib+dexamethasone) (Combination Product)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Three years after last patient first dose
To evaluate progression-free survival
Progression-Free Survival (PFS)
时间窗: From date of randomization until the date of first documented PD (per IMWG criteria) or date of death, whichever occurs first. Participants without PD or death at the time of analysis are censored at the date of their last adequate disease assessment.
To evaluate progression-free survival
次要结局
- VGPR+CR+sCR(Three years after last patient first dose)
- Progression-free survival(PFS2)(Three years after last patient first dose)
- Time to remission(TTR)(Three years after last patient first dose)
- Overall Survival (OS)(Three years after last patient first dose)
- Duration of Response (DOR)(Three years after last patient first dose)
- Objective response rate (ORR)(Three years after last patient first dose)
- Safety Endpoints(Three years after last patient first dose)
- Objective Response Rate (ORR)(From randomization until the earlier of IRC-confirmed PD or start of subsequent anti-myeloma therapy, assessed up to 2 years.)