A Study of Evaluating the Safety and Efficacy of ATG-010, Bortezomib, and Dexamethasone (SVd) Versus Bortezomib and Dexamethasone (Vd) in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Interventions
- Combination Product: Vd (Bortezomib+dexamethasone)Combination Product: SVd (Selinexor+Bortezomib+dexamethasone)
- Registration Number
- NCT04939142
- Lead Sponsor
- Antengene Corporation
- Brief Summary
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).
- Detailed Description
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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 150
-
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 2.
-
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 C1D1. 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.
- 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 C1D1.
- Major surgery within 4 weeks prior to C1D1.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vd(Bortezomib+dexamethasone) 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. SVd (Selinexor+Bortezomib+dexamethasone) 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.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Three years after last patient first dose To evaluate progression-free survival
- Secondary Outcome Measures
Name Time Method VGPR+CR+sCR Three years after last patient first dose Proportion of subjects of VGPR + CR + sCR
Progression-free survival(PFS2) Three years after last patient first dose PFS after further treatment followed by treatment with SVd/Vd
Time to remission(TTR) Three years after last patient first dose To compare the efficacy of treatment with SVd and Vd
Overall Survival (OS) Three years after last patient first dose The estimates of Kaplan-Meier
Duration of Response (DOR) Three years after last patient first dose To evaluate duration of response
Objective response rate (ORR) Three years after last patient first dose evaluated by IRC (PR + VGPR + CR + sCR)
Safety Endpoints Three years after last patient first dose Incidence of any Grade ≥ 2 peripheral neuropathy events
Trial Locations
- Locations (33)
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Shengjing Hospital China Medical University
🇨🇳Shenyang, Liaoning, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, Shandong, China
The First Affiliated Hospital OF USTC
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital of Wannan Medical College
🇨🇳Wuhu, Anhui, China
Peking University People'S Hospital
🇨🇳Beijing, Beijing, China
Beijing Chao-Yang Hospital
🇨🇳Beijing, Beijing, China
Sun Yat-Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Xinqiao Hospital Army Medical University
🇨🇳Chongqing, Chongqing, China
Guangdong Provincial People'S Hospital
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Shenzhen Second People'S Hospital
🇨🇳Shenzhen, Guangdong, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
🇨🇳Wuhan, Hubei, China
The Third Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Hospital of Nanchang
🇨🇳Nanchang, Jiangxi, China
Affiliated Hospital of Nantong University
🇨🇳Nanchang, Jiangxi, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
Qilu Hospital of Shangdong University
🇨🇳Jinan, Shangdong, China
Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Qingdao Municipal Hospital
🇨🇳Qingdao, Shandong, China
Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University
🇨🇳Shanghai, Shanghai, China
Sichuan Provincial People's Hospital
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hanzhou, Zhejiang, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital Zhejiang University of Medicine
🇨🇳Hangzhou, Zhejiang, China
Ningbo First Hospital
🇨🇳Ningbo, Zhejiang, China