<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04474938</url>
  </required_header>
  <id_info>
    <org_study_id>PUMCH-AL2020</org_study_id>
    <nct_id>NCT04474938</nct_id>
  </id_info>
  <brief_title>Daratumumab Combined With Bortezomib and Dexamethasone in Mayo 04 Stage III Light Chain Amyloidosis</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Xian-Janssen Pharmaceutical Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with light chain (AL) amyloidosis who have advanced cardiac damage are at risk of&#xD;
      premature mortality. There is ongoing unmet need for effective therapies to rapidly induce&#xD;
      deep hematologic response and decrease the early death rate. Lately, trials of daratumumab in&#xD;
      newly-diagnosed and relapsed/refractory AL amyloidosis have shown dramatic response rates.&#xD;
      However, the benefits of upfront daratumumab in stage III AL patients, especially stage IIIb&#xD;
      patients, have not yet been demonstrated definitely in prospective studies. Therefore, we&#xD;
      designed a phase II, single arm clinical trial to investigate the efficacy and safety of&#xD;
      co-administration of daratumumab with bortezomib and dexamethasone (BD) regimen in&#xD;
      treatment-naïve patients with Mayo 04 stage III AL amyloidosis. We planned to enroll 40&#xD;
      patients, who would receive daratumumab and BD treatment for a total duration of 12 months.&#xD;
      The primary endpoint is complete response and very good partial response at 3 months after&#xD;
      treatment initiation. Secondary endpoints include overall survival, organ response and&#xD;
      adverse events.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 24, 2021</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hematologic very good partial response or better at 3 months after treatment initiation</measure>
    <time_frame>3 months</time_frame>
    <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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>major organ deterioration progression-free survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to next treatment</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality within 1 month from treatment initiation</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality within 3 months from treatment initiation</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality within 6 months from treatment initiation</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic very good partial response or better at 1 month after treatment initiation</measure>
    <time_frame>1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic very good partial response or better at 6 months after treatment initiation</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematologic very good partial response or better at 12 months after treatment initiation</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stringent dFLC response</measure>
    <time_frame>1 year</time_frame>
    <description>dFLC declined to less than 10 mg/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to hematologic response</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ response at 3 months after treatment initiation</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ response at 6 months after treatment initiation</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ response at 12 months after treatment initiation</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to cardiac response</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to liver response</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to renal response</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>treatment initiation to 30 days after last dose of treatment</time_frame>
    <description>Adverse events are collected until 30 days after last dose of treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Amyloidosis; Systemic</condition>
  <arm_group>
    <arm_group_label>Dara-BD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daratumumab combined with bortezomib and dexamethasone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>16mg/kg, QW Cycles 1-2 (28 days/cycle), Q2W Cycles 3-6, and Q4W thereafter for up to 1 year</description>
    <arm_group_label>Dara-BD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>1.3mg/m2 of subcutaneous bortezomib on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles</description>
    <arm_group_label>Dara-BD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>20mg of dexamethasone on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles</description>
    <arm_group_label>Dara-BD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years old adults.&#xD;
&#xD;
               -  Biopsy proved treatment-naïve AL amyloidosis.&#xD;
&#xD;
               -  Mayo 2004 stage III.&#xD;
&#xD;
               -  dFLC &gt; 50mg/L.&#xD;
&#xD;
               -  Patient must provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-morbidity of uncontrolled infection.&#xD;
&#xD;
          -  Co-morbidity of other active malignancy.&#xD;
&#xD;
          -  Co-diagnosis of multiple myeloma or waldenstrom macroglobulinemia.&#xD;
&#xD;
          -  Co-morbidity of grade 2 or 3 atrioventricular block.&#xD;
&#xD;
          -  Co-morbidity of sustained or recurrent nonsustained ventricular tachycardia.&#xD;
&#xD;
          -  Seropositive for human immunodeficiency virus.&#xD;
&#xD;
          -  Seropositive for hepatitis B (positive test for HBsAg). Participants with resolved&#xD;
             infection (ie, HBsAg negative but positive for anti-HBc and/or anti-HBs) must be&#xD;
             screened of HBV-DNA. Those who are PCR positive will be excluded.&#xD;
&#xD;
          -  Seropositive for hepatitis C (except in the setting of a sustained virologic&#xD;
             response).&#xD;
&#xD;
          -  Grade 2 or higher neuropathy according to National Cancer Institute Common Terminology&#xD;
             Criteria for Adverse Events.&#xD;
&#xD;
          -  Neutrophil &lt;1×10E9/L，hemoglobin &lt; 7g/dL，or platelet &lt; 75×10E9/L.&#xD;
&#xD;
          -  Severely compromised hepatic or renal function: ALT or AST &gt; 2.5 × ULN, total&#xD;
             bilirubin &gt; 1.5mg/dL，or eGFR &lt; 40mL/min (those with renal dysfunction due to renal&#xD;
             involvement or renal hypoperfusion from cardiac amyloidosis could be included)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jian Li, MD</last_name>
    <role>Study Director</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>May 9, 2022</last_update_submitted>
  <last_update_submitted_qc>May 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>light chain amyloidosis</keyword>
  <keyword>daratumumab</keyword>
  <keyword>bortezomib</keyword>
  <keyword>hematologic response</keyword>
  <keyword>prognosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Daratumumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04474938
org study id: PUMCH-AL2020
nct id: NCT04474938
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hematologic very good partial response or better at 3 months after treatment initiation
time frame: 3 months
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
measure: Overall survival
time frame: 2 years
measure: major organ deterioration progression-free survival
time frame: 2 years
measure: Time to next treatment
time frame: 2 years
measure: Mortality within 1 month from treatment initiation
time frame: 1 month
measure: Mortality within 3 months from treatment initiation
time frame: 3 months
measure: Mortality within 6 months from treatment initiation
time frame: 6 months
measure: Hematologic very good partial response or better at 1 month after treatment initiation
time frame: 1 month
measure: Hematologic very good partial response or better at 6 months after treatment initiation
time frame: 6 months
measure: Hematologic very good partial response or better at 12 months after treatment initiation
time frame: 12 months
measure: Stringent dFLC response
time frame: 1 year
description: dFLC declined to less than 10 mg/L
measure: Time to hematologic response
time frame: 1 year
measure: Organ response at 3 months after treatment initiation
time frame: 3 months
measure: Organ response at 6 months after treatment initiation
time frame: 6 months
measure: Organ response at 12 months after treatment initiation
time frame: 12 months
measure: Time to cardiac response
time frame: 1 year
measure: Time to liver response
time frame: 1 year
measure: Time to renal response
time frame: 1 year
measure: Adverse events
time frame: treatment initiation to 30 days after last dose of treatment
description: Adverse events are collected until 30 days after last dose of treatment
arm group label: Dara-BD
arm group type: Experimental
description: Daratumumab combined with bortezomib and dexamethasone
intervention type: Drug
intervention name: Daratumumab
description: 16mg/kg, QW Cycles 1-2 (28 days/cycle), Q2W Cycles 3-6, and Q4W thereafter for up to 1 year
arm group label: Dara-BD
intervention type: Drug
intervention name: Bortezomib
description: 1.3mg/m2 of subcutaneous bortezomib on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles
arm group label: Dara-BD
intervention type: Drug
intervention name: Dexamethasone
description: 20mg of dexamethasone on days 1, 8, 15 and 22 of a 28-day cycle for 6 cycles
arm group label: Dara-BD
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jian Li, MD
role: Study Director
affiliation: Peking Union Medical College Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Amyloidosis
mesh term: Dexamethasone
mesh term: Bortezomib
mesh term: Daratumumab
sharing ipd: No