Venetoclax and Dexamethasone for Newly Diagnosed Light-Chain Amyloidosis With Translocation (11;14)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Complete response (CR)+very good partial response (VGPR) at 3 months after treatment initiation [3 months after treatment initiation]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
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)
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Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia
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Seropositive for human immunodeficiency virus
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Peking Union Medical College Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Ven-D001