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

Study Overview
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Brief Summary
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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.

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

Conditions
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Light Chain (AL) Amyloidosis, CCND1 Translocation, Venetoclax

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Dexamethasone Oral


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2 years | 
| Time to next treatment |  | 2 years | 
| 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 response |  | 1 year | 
| 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 |