Clinical trial NCT04474938: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Amyloidosis; Systemic
Keywords: light chain amyloidosis
daratumumab
bortezomib
hematologic response
prognosis
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Xian-Janssen Pharmaceutical Ltd.
First posted: 2020-07-17
Enrollment: 40
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: 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.


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)

Primary outcomes:
measure: Hematologic very good partial response or better at 3 months after treatment initiation
timeFrame: 3 months
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: major organ deterioration progression-free survival
timeFrame: 2 years
measure: Time to next treatment
timeFrame: 2 years
measure: Mortality within 1 month from treatment initiation
timeFrame: 1 month
measure: Mortality within 3 months from treatment initiation
timeFrame: 3 months
measure: Mortality within 6 months from treatment initiation
timeFrame: 6 months
measure: Hematologic very good partial response or better at 1 month after treatment initiation
timeFrame: 1 month
measure: Hematologic very good partial response or better at 6 months after treatment initiation
timeFrame: 6 months
measure: Hematologic very good partial response or better at 12 months after treatment initiation
timeFrame: 12 months
measure: Stringent dFLC response
timeFrame: 1 year
measure: Time to hematologic response
timeFrame: 1 year
measure: Organ response at 3 months after treatment initiation
timeFrame: 3 months
measure: Organ response at 6 months after treatment initiation
timeFrame: 6 months
measure: Organ response at 12 months after treatment initiation
timeFrame: 12 months
measure: Time to cardiac response
timeFrame: 1 year
measure: Time to liver response
timeFrame: 1 year
measure: Time to renal response
timeFrame: 1 year
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:
affiliation: Peking Union Medical College Hospital
name: Jian Li, MD
role: STUDY_DIRECTOR
References: