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

NCT04474938 | Unknown Phase 2

• 1 other identifier: PUMCH-AL2020
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Amyloidosis; Systemic

Keywords

light chain amyloidosis; daratumumab; bortezomib; hematologic response; prognosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Overall survival

  2 years

• 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

Study Arms (1)

Dara-BD

EXPERIMENTAL

Daratumumab combined with bortezomib and dexamethasone

Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Daratumumab DRUG

16mg/kg, QW Cycles 1-2 (28 days/cycle), Q2W Cycles 3-6, and Q4W thereafter for up to 1 year

Dara-BD

Bortezomib DRUG

1.3mg/m2 of subcutaneous bortezomib on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles

Dara-BD

Dexamethasone DRUG

20mg of dexamethasone on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles

Dara-BD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Xian-Janssen Pharmaceutical Ltd.: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 100730, China

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Jian Li, MD

  Peking Union Medical College Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 17, 2020
• Study Start: May 24, 2021
• Primary Completion: June 1, 2023
• Study Completion: March 1, 2024
• Last Updated: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)