Daratumumab Combined With Bortezomib and Dexamethasone in Mayo 04 Stage III Light Chain Amyloidosis
- Conditions
- Amyloidosis; Systemic
- Interventions
- Registration Number
- NCT04474938
- Lead Sponsor
- Peking Union Medical College Hospital
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
-
18 years old adults.
- Biopsy proved treatment-naïve AL amyloidosis.
- Mayo 2004 stage III.
- dFLC > 50mg/L.
- Patient must provide informed consent.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dara-BD Dexamethasone Daratumumab combined with bortezomib and dexamethasone Dara-BD Daratumumab Daratumumab combined with bortezomib and dexamethasone Dara-BD Bortezomib Daratumumab combined with bortezomib and dexamethasone
- Primary Outcome Measures
Name Time Method Hematologic very good partial response or better at 3 months after treatment initiation 3 months Very good partial response or better is defined as complete response or very good partial response. Complete response: normalization of free light chain levels and ratio with negative serum and urine immunofixation electrophoresis. Very good partial response: difference between involved and uninvolved free light chains (dFLC) less than 40 mg/L
- Secondary Outcome Measures
Name Time Method Time to liver response 1 year major organ deterioration progression-free survival 2 years Time to next treatment 2 years Mortality within 1 month from treatment initiation 1 month Mortality within 3 months from treatment initiation 3 months Mortality within 6 months from treatment initiation 6 months Hematologic very good partial response or better at 1 month after treatment initiation 1 month Time to renal response 1 year Overall survival 2 years Stringent dFLC response 1 year dFLC declined to less than 10 mg/L
Time to hematologic response 1 year Organ response at 3 months after treatment initiation 3 months Organ response at 12 months after treatment initiation 12 months Adverse events treatment initiation to 30 days after last dose of treatment Adverse events are collected until 30 days after last dose of treatment
Hematologic very good partial response or better at 6 months after treatment initiation 6 months Hematologic very good partial response or better at 12 months after treatment initiation 12 months Organ response at 6 months after treatment initiation 6 months Time to cardiac response 1 year
Trial Locations
- Locations (1)
Peking Union Medical College Hospital
🇨🇳Beijing, China