<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/NCT03768960</url>
  </required_header>
  <id_info>
    <org_study_id>CR108556</org_study_id>
    <secondary_id>54767414MMY4008</secondary_id>
    <nct_id>NCT03768960</nct_id>
  </id_info>
  <brief_title>A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent</brief_title>
  <official_title>A Prospective, Single-Arm, Multicenter, Pragmatic Phase-IV Trial Investigating Safety and Effectiveness of DARZALEX (Daratumumab) In Indian Subjects With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johnson &amp; Johnson Private Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johnson &amp; Johnson Private Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to demonstrate the safety profile of daratumumab in routine&#xD;
      clinical practice when given as monotherapy in Indian participants with relapsed and&#xD;
      refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an&#xD;
      immunomodulatory agent.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 10, 2019</start_date>
  <completion_date type="Actual">July 16, 2022</completion_date>
  <primary_completion_date type="Actual">July 16, 2022</primary_completion_date>
  <phase>Phase 4</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>Incidence of Treatment Emergent Adverse Events (TEAE)</measure>
    <time_frame>Approximately up to 29 weeks</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Approximately up to 24 weeks</time_frame>
    <description>ORR- % of participants who achieve partial response (PR) or better per IMWG criteria during study treatment. PR: &gt;=50% reduction of serum M-protein, &gt;=90% reduction in 24 hour urinary M-protein or to&lt;200mg/24hour; if serum and urine M-protein are not measurable, &gt;=50% decrease in difference between involved and uninvolved free light chain (FLC) level; if serum and urine M-protein and serum free light assay is not measurable, &gt;=50% reduction in bone marrow plasma cell (PC), with baseline bone marrow PC% &gt;=30%; if present at baseline, &gt;=50% reduction in size of soft tissue plasmacytomas; VGPR: serum and urine M-component detectable by immunofixation or &gt;=90% reduction in serum M-protein and urine M-protein &lt;100mg/24hour; Complete response(CR):negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt;5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Very Good Partial Response (VGPR) or better</measure>
    <time_frame>Approximately up to 24 weeks</time_frame>
    <description>VGPR or better is defined as percentage (%) of participants with a response of very good partial response (VGPR) or better according to the International Myeloma Working Group (IMWG) criteria, during the study treatment. IMWG criteria for VGPR: serum and urine M-component detectable by immunofixation or greater than or equal to (&gt;=)90% reduction in serum M-protein and urine M-protein less than (&lt;)100 milligram(mg)/24hour; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and &lt;5% PCs in bone marrow; Stringent CR (sCR): CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Progression Free Survival (PFS)</measure>
    <time_frame>Approximately up to 24 weeks</time_frame>
    <description>PFS is defined as % of participants with PFS from date of randomization to either PD, according to the IMWG criteria or death, whichever occurs first. PD: Increase of &gt;=25% in level of serum M-protein from lowest response value and absolute increase must be &gt;=0.5 gram per deciliter (g/dL); Increase of &gt;=25% in 24 hours urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be &gt;=200 mg/24 hour; Only in participants without measurable serum and urine M-protein levels: increase of &gt;=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be greater than (&gt;)10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium &gt;11.5 mg/dL) that can be attributed solely to PC proliferative disorder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response</measure>
    <time_frame>Approximately up to 24 weeks</time_frame>
    <description>Time to Response: time between the date of randomization and the first effectiveness evaluation that the participant has met all criteria for CR or PR. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and &lt;5% PCs in bone marrow; PR: greater than or equal to (&gt;=) 50% reduction of serum M-protein, &gt;=90% reduction in 24 hour urinary M-protein or to less than (&lt;) 200 mg/24 hours; if serum and urine M-protein are not measurable, &gt;=50% decrease in difference between involved and uninvolved free light chains (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, &gt;=50% reduction in bone marrow plasma cell (PC), with baseline bone marrow PC percentage &gt;=30%; if present at baseline, &gt;=50% reduction in size of soft tissue plasmacytomas.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score</measure>
    <time_frame>Baseline, Day 1 (Cycle 1 to 5); Days 1 and 28 (Cycle 6) (each cycle of 28 days)</time_frame>
    <description>The EORTC QLQ-C30 is a 30-item questionnaire containing both single and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/ Quality-of-Life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). The scores ranges from 0-100, a high score for functional scales and for Global Health Status/QoL represent better functioning ability or Health-Related Quality-of-Life (HRQoL), whereas a high score for symptom scales and single items represents significant symptomatology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in EuroQol-5 Dimensions (EQ-5D-5L) Score</measure>
    <time_frame>Baseline, Day 1 (Cycle 1 to 5); Days 1 and 28 (Cycle 6) (each cycle of 28 days)</time_frame>
    <description>EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating &quot;health today&quot; with ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The responses to the 5 dimensions are used to compute a single utility score ranging from zero (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Daratumumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 16 milligram per kilogram (mg/kg) of daratumumab as intravenous (IV) infusion every week (QW) in Cycles 1 and 2 (Days 1, 8, 15 and 22) and every 2 weeks (Q2W) in Cycle 3 to 6 (Days 1 and 15) each cycle is of 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>Participants will receive 16 mg/kg of daratumumab as IV infusion QW in Cycles 1 and 2 (Days 1, 8, 15 and 22) and Q2W in Cycle 3 to 6 (Days 1 and 15).</description>
    <arm_group_label>Daratumumab</arm_group_label>
    <other_name>DARZALEX</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with relapsed and refractory multiple myeloma (as per International&#xD;
             Myeloma Working Group [IMWG] definitions) whose prior therapy included a proteasome&#xD;
             inhibitor and an immunomodulatory agent, being newly initiated on DARZALEX&#xD;
             (daratumumab) monotherapy based on independent clinical judgment of treating&#xD;
             physicians as per locally approved prescribing information&#xD;
&#xD;
          -  Each participant (or their legally acceptable representative) must sign an informed&#xD;
             consent form (ICF) indicating that he or she understands the purpose of and procedures&#xD;
             required for the study and are willing to participate in the study. Participants must&#xD;
             be willing and able to adhere to the prohibitions and restrictions specified in this&#xD;
             protocol, as referenced in the informed consent form (ICF)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who are not eligible to receive DARZALEX as per the locally approved&#xD;
             prescribing information&#xD;
&#xD;
          -  Participant participating or planning to participate in any interventional drug trial&#xD;
             during the course of this study&#xD;
&#xD;
          -  Known seropositive for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Seropositive for hepatitis B (defined by a positive test for hepatitis B surface&#xD;
             antigen [HBsAg]). Participants with resolved infection (that is, participants who are&#xD;
             HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc]&#xD;
             and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using&#xD;
             real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV)&#xD;
             deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded.&#xD;
             exception: Participants with serologic findings suggestive of HBV vaccination&#xD;
             (anti-HBs positivity as the only serologic marker) and a known history of prior HBV&#xD;
             vaccination, do not need to be tested for HBV DNA by PCR&#xD;
&#xD;
          -  Known seropositive for hepatitis C (except in the setting of a sustained virologic&#xD;
             response [SVR], defined as aviremia at least 12 weeks after completion of antiviral&#xD;
             therapy)&#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>Johnson &amp; Johnson Private Limited Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Johnson &amp; Johnson Private Limited</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Avron Hospitals Pvt. Ltd</name>
      <address>
        <city>Ahmedabad</city>
        <zip>380013</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M S Ramaiah Medical College and Hospital</name>
      <address>
        <city>Bengaluru</city>
        <zip>560054</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sparsh Hospitals &amp; Critical Care (Pvt) Ltd</name>
      <address>
        <city>Bhubaneshwar</city>
        <zip>751007</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Apollo Hospitals</name>
      <address>
        <city>Bhubaneswar</city>
        <zip>751005</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Post Graduate Institute of Medical Education &amp; Research (PGIMER)</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Apollo Hospitals</name>
      <address>
        <city>Hyderabad</city>
        <zip>500033</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Basavatarakam Indo-American Hospital</name>
      <address>
        <city>Hyderabad</city>
        <zip>500034</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cytecare Hospitals Pvt. Ltd</name>
      <address>
        <city>Karnataka</city>
        <zip>560064</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tata Medical Center</name>
      <address>
        <city>Kolkata</city>
        <zip>700156</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shatabdi Super Speciality Hospital</name>
      <address>
        <city>Mumbai Naka</city>
        <zip>422005</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingsway Hospital</name>
      <address>
        <city>Nagpur</city>
        <zip>440001</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Apex Wellness Hospital</name>
      <address>
        <city>Nashik</city>
        <zip>422009</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>All India Institute of Medical Sciences</name>
      <address>
        <city>New Delhi</city>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jawaharlal Institute of Postgraduate Medical Education and Research</name>
      <address>
        <city>Pondicherry</city>
        <zip>605008</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deenanath Mangeshkar Hospital and Research Centre</name>
      <address>
        <city>Pune</city>
        <zip>411004</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Noble Hospital Pvt Ltd</name>
      <address>
        <city>Pune</city>
        <zip>411013</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>August 15, 2022</last_update_submitted>
  <last_update_submitted_qc>August 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Daratumumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03768960
org study id: CR108556
secondary id: 54767414MMY4008
nct id: NCT03768960
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to demonstrate the safety profile of daratumumab in routine
      clinical practice when given as monotherapy in Indian participants with relapsed and
      refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an
      immunomodulatory agent.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment Emergent Adverse Events (TEAE)
time frame: Approximately up to 29 weeks
description: An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug.
measure: Overall Response Rate (ORR)
time frame: Approximately up to 24 weeks
description: ORR- % of participants who achieve partial response (PR) or better per IMWG criteria during study treatment. PR: >=50% reduction of serum M-protein, >=90% reduction in 24 hour urinary M-protein or to<200mg/24hour; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) level; if serum and urine M-protein and serum free light assay is not measurable, >=50% reduction in bone marrow plasma cell (PC), with baseline bone marrow PC% >=30%; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; VGPR: serum and urine M-component detectable by immunofixation or >=90% reduction in serum M-protein and urine M-protein <100mg/24hour; Complete response(CR):negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.
measure: Percentage of Participants with Very Good Partial Response (VGPR) or better
time frame: Approximately up to 24 weeks
description: VGPR or better is defined as percentage (%) of participants with a response of very good partial response (VGPR) or better according to the International Myeloma Working Group (IMWG) criteria, during the study treatment. IMWG criteria for VGPR: serum and urine M-component detectable by immunofixation or greater than or equal to (>=)90% reduction in serum M-protein and urine M-protein less than (<)100 milligram(mg)/24hour; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; Stringent CR (sCR): CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.
measure: Percentage of Participants with Progression Free Survival (PFS)
time frame: Approximately up to 24 weeks
description: PFS is defined as % of participants with PFS from date of randomization to either PD, according to the IMWG criteria or death, whichever occurs first. PD: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 gram per deciliter (g/dL); Increase of >=25% in 24 hours urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24 hour; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be greater than (>)10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
measure: Time to Response
time frame: Approximately up to 24 weeks
description: Time to Response: time between the date of randomization and the first effectiveness evaluation that the participant has met all criteria for CR or PR. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% PCs in bone marrow; PR: greater than or equal to (>=) 50% reduction of serum M-protein, >=90% reduction in 24 hour urinary M-protein or to less than (<) 200 mg/24 hours; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chains (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, >=50% reduction in bone marrow plasma cell (PC), with baseline bone marrow PC percentage >=30%; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas.
measure: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
time frame: Baseline, Day 1 (Cycle 1 to 5); Days 1 and 28 (Cycle 6) (each cycle of 28 days)
description: The EORTC QLQ-C30 is a 30-item questionnaire containing both single and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/ Quality-of-Life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). The scores ranges from 0-100, a high score for functional scales and for Global Health Status/QoL represent better functioning ability or Health-Related Quality-of-Life (HRQoL), whereas a high score for symptom scales and single items represents significant symptomatology.
measure: Change from Baseline in EuroQol-5 Dimensions (EQ-5D-5L) Score
time frame: Baseline, Day 1 (Cycle 1 to 5); Days 1 and 28 (Cycle 6) (each cycle of 28 days)
description: EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The responses to the 5 dimensions are used to compute a single utility score ranging from zero (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual.
arm group label: Daratumumab
arm group type: Experimental
description: Participants will receive 16 milligram per kilogram (mg/kg) of daratumumab as intravenous (IV) infusion every week (QW) in Cycles 1 and 2 (Days 1, 8, 15 and 22) and every 2 weeks (Q2W) in Cycle 3 to 6 (Days 1 and 15) each cycle is of 28 days.
intervention type: Drug
intervention name: Daratumumab
description: Participants will receive 16 mg/kg of daratumumab as IV infusion QW in Cycles 1 and 2 (Days 1, 8, 15 and 22) and Q2W in Cycle 3 to 6 (Days 1 and 15).
arm group label: Daratumumab
other name: DARZALEX
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johnson & Johnson Private Limited Clinical Trial
role: Study Director
affiliation: Johnson & Johnson Private Limited
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: India
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Daratumumab