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

Phase 2Active Not RecruitingNCT05996406

Peking Union Medical College Hospital36 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Light Chain (AL) Amyloidosis CCND1 Translocation Venetoclax

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 3 months after treatment initiation

Secondary Outcomes

Overall survival

Time frame: 2 years

Time to next treatment

Time frame: 2 years

CR+VGPR at 1 month after treatment initiation

Time frame: 1 month after treatment initiation

CR+VGPR at 6 months after treatment initiation

Time frame: 6 months after treatment initiation

CR+VGPR at 12 months after treatment initiation

Time frame: 12 months after treatment initiation

Difference between involved and uninvolved free light chain (dFLC) < 10mg/L

Time frame: at 1, 3, 6 and 12 months after treatment initiation

Involved free light chain (iFLC) ≤ 20mg/L

Time frame: at 1, 3, 6 and 12 months after treatment initiation

Minimal residual disease (MRD) negativity

Time frame: 12 and 24 months after treatment initiation

Time to hematologic response

Time frame: 1 year

Time to hematologic CR

Time frame: 1 year

Cardiac response

Time frame: at 3, 6, 12 and 24 months after treatment initiation

Renal response

Time frame: at 3, 6, 12 and 24 months after treatment initiation

Hepatic response

Time frame: at 3, 6, 12 and 24 months after treatment initiation

Time to cardiac response

Time frame: 2 years

Time to renal response

Time frame: 2 years

Time to hepatic response

Time frame: 2 years

Adverse events

Time frame: treatment initiation to 30 days after last dose of treatment

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes