Back to resultsDaratumumab Combined With Bortezomib and Dexamethasone in Mayo 04 Stage III Light Chain Amyloidosis
Primary Purpose
Amyloidosis; Systemic
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Daratumumab
Bortezomib
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Amyloidosis; Systemic focused on measuring light chain amyloidosis, daratumumab, bortezomib, hematologic response, prognosis
Eligibility Criteria
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)
Sites / Locations
- Peking Union Medical College Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dara-BD
Arm Description
Daratumumab combined with bortezomib and dexamethasone
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Overall survival
major organ deterioration progression-free survival
Time to next treatment
Mortality within 1 month from treatment initiation
Mortality within 3 months from treatment initiation
Mortality within 6 months from treatment initiation
Hematologic very good partial response or better at 1 month after treatment initiation
Hematologic very good partial response or better at 6 months after treatment initiation
Hematologic very good partial response or better at 12 months after treatment initiation
Stringent dFLC response
dFLC declined to less than 10 mg/L
Time to hematologic response
Organ response at 3 months after treatment initiation
Organ response at 6 months after treatment initiation
Organ response at 12 months after treatment initiation
Time to cardiac response
Time to liver response
Time to renal response
Adverse events
Adverse events are collected until 30 days after last dose of treatment
Full Information
NCT ID
NCT04474938
First Posted
July 14, 2020
Last Updated
May 9, 2022
Sponsor
Peking Union Medical College Hospital
Collaborators
Xian-Janssen Pharmaceutical Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04474938
Brief Title
Daratumumab Combined With Bortezomib and Dexamethasone in Mayo 04 Stage III Light Chain Amyloidosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 24, 2021 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Xian-Janssen Pharmaceutical Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis; Systemic
Keywords
light chain amyloidosis, daratumumab, bortezomib, hematologic response, prognosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dara-BD
Arm Type
Experimental
Arm Description
Daratumumab combined with bortezomib and dexamethasone
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Intervention Description
16mg/kg, QW Cycles 1-2 (28 days/cycle), Q2W Cycles 3-6, and Q4W thereafter for up to 1 year
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
1.3mg/m2 of subcutaneous bortezomib on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
20mg of dexamethasone on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles
Primary Outcome Measure Information:
Title
Hematologic very good partial response or better at 3 months after treatment initiation
Description
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
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
2 years
Title
major organ deterioration progression-free survival
Time Frame
2 years
Title
Time to next treatment
Time Frame
2 years
Title
Mortality within 1 month from treatment initiation
Time Frame
1 month
Title
Mortality within 3 months from treatment initiation
Time Frame
3 months
Title
Mortality within 6 months from treatment initiation
Time Frame
6 months
Title
Hematologic very good partial response or better at 1 month after treatment initiation
Time Frame
1 month
Title
Hematologic very good partial response or better at 6 months after treatment initiation
Time Frame
6 months
Title
Hematologic very good partial response or better at 12 months after treatment initiation
Time Frame
12 months
Title
Stringent dFLC response
Description
dFLC declined to less than 10 mg/L
Time Frame
1 year
Title
Time to hematologic response
Time Frame
1 year
Title
Organ response at 3 months after treatment initiation
Time Frame
3 months
Title
Organ response at 6 months after treatment initiation
Time Frame
6 months
Title
Organ response at 12 months after treatment initiation
Time Frame
12 months
Title
Time to cardiac response
Time Frame
1 year
Title
Time to liver response
Time Frame
1 year
Title
Time to renal response
Time Frame
1 year
Title
Adverse events
Description
Adverse events are collected until 30 days after last dose of treatment
Time Frame
treatment initiation to 30 days after last dose of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jian Li, MD
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100730
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Daratumumab Combined With Bortezomib and Dexamethasone in Mayo 04 Stage III Light Chain Amyloidosis
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