Daratumumab Combined With Bortezomib and Dexamethasone in Mayo 04 Stage III Light Chain Amyloidosis

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase

Unknown

Phase 2

Conditions

Amyloidosis; Systemic

Treatments

Drug: Daratumumab

Drug: Dexamethasone

Drug: Bortezomib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04474938

PUMCH-AL2020

Details and patient eligibility

About

Patients with light chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. There is ongoing unmet need for effective therapies to rapidly induce deep hematologic response and decrease the early death rate. Lately, trials of daratumumab in newly-diagnosed and relapsed/refractory AL amyloidosis have shown dramatic response rates. However, the benefits of upfront daratumumab in stage III AL patients, especially stage IIIb patients, have not yet been demonstrated definitely in prospective studies. Therefore, we designed a phase II, single arm clinical trial to investigate the efficacy and safety of co-administration of daratumumab with bortezomib and dexamethasone (BD) regimen in treatment-naïve patients with Mayo 04 stage III AL amyloidosis. We planned to enroll 40 patients, who would receive daratumumab and BD treatment for a total duration of 12 months. The primary endpoint is complete response and very good partial response at 3 months after treatment initiation. Secondary endpoints include overall survival, organ response and adverse events.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

18 years old adults.
- Biopsy proved treatment-naïve AL amyloidosis.
- Mayo 2004 stage III.
- dFLC > 50mg/L.
- Patient must provide informed consent.

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 or 3 atrioventricular block.
Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia.
Seropositive for human immunodeficiency virus.
Seropositive for hepatitis B (positive test for HBsAg). Participants with resolved infection (ie, HBsAg negative but positive for anti-HBc and/or anti-HBs) must be screened of HBV-DNA. Those who are PCR positive will be excluded.
Seropositive for hepatitis C (except in the setting of a sustained virologic response).
Grade 2 or higher neuropathy according to National Cancer Institute Common Terminology Criteria for Adverse Events.
Neutrophil <1×10E9/L，hemoglobin < 7g/dL，or platelet < 75×10E9/L.
Severely compromised hepatic or renal function: ALT or AST > 2.5 × ULN, total bilirubin > 1.5mg/dL，or eGFR < 40mL/min (those with renal dysfunction due to renal involvement or renal hypoperfusion from cardiac amyloidosis could be included)