Clinical trial NCT04939142: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Relapsed or Refractory Multiple Myeloma
Lead sponsor: Antengene Corporation
Sponsor class: INDUSTRY
First posted: 2021-06-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form (ICF).
2. Age ≥ 18 years.
3. Confirmed MM with measurable disease per IMWG guidelines, and meet at least 1 of the following:

   1. 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
   2. Urinary M-protein level ≥ 200 mg/24 hours; or
   3. Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal (Normal FLC ratio: 0.26 to 1.65).
4. 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.
5. Valid evidence of progressive MM (based on the Investigator's determination according to the IMWG response criteria) on or after their last regimen.
6. Must have an ECOG Status score of 0, 1, or 2.
7. Renal function should meet the following criteria: creatinine clearance \[CrCl\] rates ≥ 20 mL/min (Calculated using the formula of Cockroft and Gault).
8. 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.
9. 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.

Exclusion Criteria:

1. Prior exposure to SINE compounds (Including ATG-010), or suspected allergy to SINE or similar drugs.
2. Active plasma cell leukemia.
3. Documented systemic light chain amyloidosis.
4. MM involving the central nervous system.
5. POEMS syndrome (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes).
6. Spinal cord compression related to MM.
7. Greater than Grade 2 peripheral neuropathy or Grade ≥ 2 peripheral neuropathy with pain at baseline, regardless of whether the subject is currently receiving medication.
8. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
9. Active graft versus host disease (After allogeneic stem cell transplantation) at screening.
10. Uncontrolled active infections requiring intravenous antibiotics, antivirals, or antifungal therapy in 2 weeks prior to C1D1.
11. Major surgery within 4 weeks prior to C1D1.
12. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
13. 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).
14. Pregnant or lactating women.
15. Life expectancy of \< 4 months.
16. 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.
17. 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.
18. Contraindication to any of the required concomitant drugs or supportive treatments.
19. Any diseases or complications which may interfere with the study procedures.
20. Subject unwilling or unable to comply with the protocol.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Three years after last patient first dose
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Three years after last patient first dose
measure: Duration of Response (DOR)
timeFrame: Three years after last patient first dose
measure: Objective response rate (ORR)
timeFrame: Three years after last patient first dose
measure: Progression-free survival(PFS2)
timeFrame: Three years after last patient first dose
measure: Time to remission(TTR)
timeFrame: Three years after last patient first dose
measure: VGPR+CR+sCR
timeFrame: Three years after last patient first dose
measure: Safety Endpoints
timeFrame: Three years after last patient first dose
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital OF USTC
state: Anhui
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People'S Hospital
state: Beijing
city: Chongqing
country: China
facility: Xinqiao Hospital Army Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Guangdong Provincial People'S Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People'S Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: Affiliated Hospital of Nantong University
state: Jiangxi
city: Nanchang
country: China
facility: The First Hospital of Nanchang
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shangdong University
state: Shangdong
city: Shanghai
country: China
facility: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University of Medicine
state: Zhejiang
city: Hanzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
Study officials:
affiliation: Peking University People's Hospital
name: Jin Lu, PhD
role: PRINCIPAL_INVESTIGATOR
References: