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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2

Conditions: Light Chain (AL) Amyloidosis

Treatments: Drug: Daratumumab 16 mg/kg (intravenous) or Daratumumab 1800mg (subcutaneous); Drug: Dexamethasone; Drug: Venetoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT06629818

Dara-VenD001

Details and patient eligibility

About

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 combined with daratumumab and dexamethasone in untreated AL amyloidosis patients.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Dara-VenD

Experimental group

Description:

Daratumumab combined with venetoclax and dexamethasone

Treatment:

Drug: Dexamethasone

Drug: Venetoclax

Drug: Daratumumab 16 mg/kg (intravenous) or Daratumumab 1800mg (subcutaneous)