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)

Relapsed or Refractory Multiple Myeloma Clinical Trial

— BENCH  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04939142
• Other study ID #: ATG-010-MM-002
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 12, 2021
• Est. completion date: October 15, 2024

Study information

• Verified date: April 2024
• Source: Antengene Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: October 15, 2024
• Est. primary completion date: July 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Combination Product:
• SVd (Selinexor+Bortezomib+dexamethasone)
Randomized into two treatment Arms in a 2:1 allocation (SVd Arm or Vd Arm): (1) SVd Arm (~100): ATG-010 + (Once a week, QW) + bortezomib (QW) + dexamethasone (BIW)
• Vd (Bortezomib+dexamethasone)
Vd Arm (~50): Bortezomib (Cycles 1-8 [BIW], Cycles = 9 [QW]) + dexamethasone (Cycles 1-8 [Four times a week], Cycles = 9 [BIW])

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital	Beijing	Beijing
China	Peking University People'S Hospital	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Xinqiao Hospital Army Medical University	Chongqing	Chongqing
China	Guangdong Provincial People'S Hospital	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital Zhejiang University of Medicine	Hangzhou	Zhejiang
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hanzhou	Zhejiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The First Affiliated Hospital OF USTC	Hefei	Anhui
China	Qilu Hospital of Shangdong University	Jinan	Shangdong
China	Shandong Provincial Hospital	Jinan	Shandong
China	Affiliated Hospital of Nantong University	Nanchang	Jiangxi
China	The First Hospital of Nanchang	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Ningbo First Hospital	Ningbo	Zhejiang
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Shengjing Hospital China Medical University	Shenyang	Liaoning
China	Shenzhen Second People'S Hospital	Shenzhen	Guangdong
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei
China	The First Affiliated Hospital of Wannan Medical College	Wuhu	Anhui
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Antengene Corporation

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	To evaluate progression-free survival	Three years after last patient first dose
Secondary	Overall Survival (OS)	The estimates of Kaplan-Meier	Three years after last patient first dose
Secondary	Duration of Response (DOR)	To evaluate duration of response	Three years after last patient first dose
Secondary	Objective response rate (ORR)	evaluated by IRC (PR + VGPR + CR + sCR)	Three years after last patient first dose
Secondary	Progression-free survival(PFS2)	PFS after further treatment followed by treatment with SVd/Vd	Three years after last patient first dose
Secondary	Time to remission(TTR)	To compare the efficacy of treatment with SVd and Vd	Three years after last patient first dose
Secondary	VGPR+CR+sCR	Proportion of subjects of VGPR + CR + sCR	Three years after last patient first dose
Secondary	Safety Endpoints	Incidence of any Grade = 2 peripheral neuropathy events	Three years after last patient first dose