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

NCT06629818 | Recruiting Phase 2 DMC

• 1 other identifier: Dara-VenD001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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 combined with daratumumab and dexamethasone in untreated AL amyloidosis patients.

Conditions

Light Chain (AL) Amyloidosis

Keywords

Light Chain (AL) Amyloidosis; CCND1 Translocation; Venetoclax; Daratumumab

Outcome Measures

Primary Outcomes (1)

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

  3 months after treatment initiation

Secondary Outcomes (17)

• 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

Study Arms (1)

Dara-VenD

EXPERIMENTAL

Daratumumab combined with venetoclax and dexamethasone

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

Interventions

Daratumumab 16 mg/kg (intravenous) or Daratumumab 1800mg (subcutaneous) DRUG

qw cycle 1-2, q2w cycle 3-6, q4w cycle 7-12

Dara-VenD

Venetoclax DRUG

400mg po qd for 1 year

Dara-VenD

Dexamethasone DRUG

Dexamethasone 20mg po qw for the first 6 months, then 10mg po qw for the next 6 months

Dara-VenD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy proved treatment-naïve AL amyloidosis
• Fluorescence in situ hybridization (FISH) t(11;14) ≥ 10%
• dFLC \> 50mg/L

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Amyloidosis

Interventions

daratumumab; Injections, Subcutaneous; venetoclax; Dexamethasone

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Kaini Shen

CONTACT

86-13693339884; shenkaini3@sina.com

Jian Li

CONTACT

86-18610852525; lijan@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: October 8, 2024
• Study Start: October 15, 2024
• Primary Completion (Estimated): October 14, 2026
• Study Completion (Estimated): October 14, 2026
• Last Updated: June 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)