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

Phase 2

Active, not recruiting

• Conditions: Light Chain (AL) Amyloidosis; CCND1 Translocation; Venetoclax
• Interventions: Drug: Venetoclax; Drug: Dexamethasone Oral

• Registration Number: NCT05996406
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-09
• Study First Submitted QC: 2023-08-16
• Study First Posted: 2023-08-18
• Study Start: 2023-09-07
• Primary Completion: 2024-11-13
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-19
• Last Update Posted: 2025-01-22
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ven-D	Dexamethasone Oral	Venetoclax combined with dexamethasone
Ven-D	Venetoclax	Venetoclax combined with dexamethasone

Primary Outcome Measures

Name	Time	Method
Complete response (CR)+very good partial response (VGPR) at 3 months after treatment initiation	3 months after treatment initiation

Secondary Outcome Measures

Name	Time	Method
Overall survival	2 years
Time to next treatment	2 years
Time to hematologic CR	1 year
Time to cardiac response	2 years
Time to renal response	2 years
Time to hepatic response	2 years
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 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
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
Adverse events	treatment initiation to 30 days after last dose of treatment

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China