Venetoclax and Dexamethasone for Newly Diagnosed Light-Chain Amyloidosis With Translocation (11;14)

Venetoclax Combined With Dexamethasone for Newly Diagnosed Light-Chain Amyloidosis Patients With Translocation (11;14): A Multicenter Phase 2 Study

Venetoclax is considered as a promising agent for light-chain (AL) amyloidosis due to the high percentage of t(11;14). Several retrospective studies showed venetoclax-based therapy could induce rapid and profound hematologic response in AL patients with favorable safety profile. As an oral agent with encouraging data, it is worth to prospectively evaluate the efficacy and safety of venetoclax in untreated AL amyloidosis patients.

Study Overview

• Status: Recruiting
• Conditions: Light Chain (AL) Amyloidosis; Venetoclax; CCND1 Translocation
• Intervention / Treatment: Drug: Venetoclax; Drug: Dexamethasone Oral

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kaini Shen, Dr.; Phone Number: +86 13693339884; Email: shenkaini3@sina.com
• Study Contact Backup: Name: Jian Li; Phone Number: +86 18610852525; Email: lijian@pumch.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Kaini Shen; Email: shenkaini3@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy proved treatment-naïve AL amyloidosis
• Fluorescence in situ hybridization (FISH) t(11;14) ≥ 10%
• dFLC > 50mg/L

Exclusion Criteria:

• Co-morbidity of uncontrolled infection
• Co-morbidity of other active malignancy
• Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia
• Co-morbidity of grade 2 Mobitz II or grade 3 atrioventricular block (expect for those with implanted pacemaker)
• Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia
• Seropositive for human immunodeficiency virus
• Hepatitis B virus (HBV)-DNA > 1000 copies/mL
• Seropositive for hepatitis C (except in the setting of a sustained virologic response)
• Systemic treatment with moderate or strong cytochrome P450 3A （CYP3A） inducers, moderate or strong CYP3A inhibitors within 7 days prior to the first dose of study drug
• Neutrophil <1×10E9/L，hemoglobin < 8g/dL，or platelet < 100×10E9/L.
• Severely compromised hepatic or renal function: alanine transaminase (ALT) or aspertate aminotransferase (AST) > 2.5 × upper limit of normal (ULN), total bilirubin > 3 × ULN，eGFR < 15 mL/min, or receiving renal replacement therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ven-D; Venetoclax combined with dexamethasone	Drug: Venetoclax; Venetoclax 400mg po qd for 1 year; Drug: Dexamethasone Oral; Dexamethasone 40mg po qw for the first 6 months, then 10mg po qw for the next 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response (CR)+very good partial response (VGPR) at 3 months after treatment initiation	3 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	2 years
Time to next treatment	2 years
Time to hematologic response	1 year
CR+VGPR at 1 month after treatment initiation	1 month after treatment initiation
CR+VGPR at 6 months after treatment initiation	6 months after treatment initiation
CR+VGPR at 12 months after treatment initiation	12 months after treatment initiation
Difference between involved and uninvolved free light chain (dFLC) < 10mg/L	at 1, 3, 6 and 12 months after treatment initiation
Involved free light chain (iFLC) ≤ 20mg/L	at 1, 3, 6 and 12 months after treatment initiation
Minimal residual disease (MRD) negativity	12 and 24 months after treatment initiation
Time to hematologic CR	1 year
Cardiac response	at 3, 6, 12 and 24 months after treatment initiation
Renal response	at 3, 6, 12 and 24 months after treatment initiation
Hepatic response	at 3, 6, 12 and 24 months after treatment initiation
Time to cardiac response	2 years
Time to renal response	2 years
Time to hepatic response	2 years
Adverse events	treatment initiation to 30 days after last dose of treatment

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 9, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Venetoclax
• Other Study ID Numbers: Ven-D001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No