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

Amyloidosis; Systemic Clinical Trial

Official title:

Efficacy of Daratumumab Combined With Bortezomib and Dexamethasone in Patients With Mayo 04 Stage III Light Chain Amyloidosis: a Prospective Phase II Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04474938
• Other study ID #: PUMCH-AL2020
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 24, 2021
• Est. completion date: March 2024

Study information

• Verified date: May 2022
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: March 2024
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Amyloidosis
• Amyloidosis; Systemic

Intervention

Drug:
• Daratumumab
16mg/kg, QW Cycles 1-2 (28 days/cycle), Q2W Cycles 3-6, and Q4W thereafter for up to 1 year
• Bortezomib
1.3mg/m2 of subcutaneous bortezomib on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles
• Dexamethasone
20mg of dexamethasone on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Xian-Janssen Pharmaceutical Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematologic very good partial response or better at 3 months after treatment initiation	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	3 months
Secondary	Overall survival		2 years
Secondary	major organ deterioration progression-free survival		2 years
Secondary	Time to next treatment		2 years
Secondary	Mortality within 1 month from treatment initiation		1 month
Secondary	Mortality within 3 months from treatment initiation		3 months
Secondary	Mortality within 6 months from treatment initiation		6 months
Secondary	Hematologic very good partial response or better at 1 month after treatment initiation		1 month
Secondary	Hematologic very good partial response or better at 6 months after treatment initiation		6 months
Secondary	Hematologic very good partial response or better at 12 months after treatment initiation		12 months
Secondary	Stringent dFLC response	dFLC declined to less than 10 mg/L	1 year
Secondary	Time to hematologic response		1 year
Secondary	Organ response at 3 months after treatment initiation		3 months
Secondary	Organ response at 6 months after treatment initiation		6 months
Secondary	Organ response at 12 months after treatment initiation		12 months
Secondary	Time to cardiac response		1 year
Secondary	Time to liver response		1 year
Secondary	Time to renal response		1 year
Secondary	Adverse events	Adverse events are collected until 30 days after last dose of treatment	treatment initiation to 30 days after last dose of treatment