Clinical trial NCT05996406: Venetoclax and Dexamethasone for Newly Diagnosed Light-Chain Amyloidosis with Translocation (11;14)
Official title: Venetoclax Combined with Dexamethasone for Newly Diagnosed Light-Chain Amyloidosis Patients with Translocation (11;14): a Multicenter Phase 2 Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Light Chain (AL) Amyloidosis
CCND1 Translocation
Venetoclax
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-08-18
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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)
* 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

Primary outcomes:
measure: Complete response (CR)+very good partial response (VGPR) at 3 months after treatment initiation
timeFrame: 3 months after treatment initiation
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Time to next treatment
timeFrame: 2 years
measure: CR+VGPR at 1 month after treatment initiation
timeFrame: 1 month after treatment initiation
measure: CR+VGPR at 6 months after treatment initiation
timeFrame: 6 months after treatment initiation
measure: CR+VGPR at 12 months after treatment initiation
timeFrame: 12 months after treatment initiation
measure: Difference between involved and uninvolved free light chain (dFLC) < 10mg/L
timeFrame: at 1, 3, 6 and 12 months after treatment initiation
measure: Involved free light chain (iFLC) ≤ 20mg/L
timeFrame: at 1, 3, 6 and 12 months after treatment initiation
measure: Minimal residual disease (MRD) negativity
timeFrame: 12 and 24 months after treatment initiation
measure: Time to hematologic response
timeFrame: 1 year
measure: Time to hematologic CR
timeFrame: 1 year
measure: Cardiac response
timeFrame: at 3, 6, 12 and 24 months after treatment initiation
measure: Renal response
timeFrame: at 3, 6, 12 and 24 months after treatment initiation
measure: Hepatic response
timeFrame: at 3, 6, 12 and 24 months after treatment initiation
measure: Time to cardiac response
timeFrame: 2 years
measure: Time to renal response
timeFrame: 2 years
measure: Time to hepatic response
timeFrame: 2 years
measure: Adverse events
timeFrame: treatment initiation to 30 days after last dose of treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
References: