<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/NCT03301220</url>
  </required_header>
  <id_info>
    <org_study_id>CR108172</org_study_id>
    <secondary_id>54767414SMM3001</secondary_id>
    <secondary_id>2016-001205-16</secondary_id>
    <nct_id>NCT03301220</nct_id>
  </id_info>
  <brief_title>A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma</brief_title>
  <official_title>A Phase 3 Randomized, Multicenter Study of Subcutaneous Daratumumab Versus Active Monitoring in Subjects With High-Risk Smoldering Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine whether treatment with daratumumab&#xD;
      administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with&#xD;
      active monitoring in participants with high-risk smoldering multiple myeloma (SMM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study consists of 3 phases: Screening Phase (up to 35 days), an Active Monitoring Phase&#xD;
      or a Treatment Phase of 39 cycles or 36 months (whichever occurs first), and a Follow-up&#xD;
      Phase which will continue until death, lost to follow-up, consent withdrawal, or study end&#xD;
      (approximately 8 years after the first participant is randomized), whichever occurs first.&#xD;
      Active monitoring cycles and treatment cycles are 4 weeks in length. For all participants,&#xD;
      disease evaluations will be performed every 12 weeks until confirmed progressive disease&#xD;
      (PD). After PD, survival is to be followed at least every 6 months, until the end of the&#xD;
      study. Participants will undergo tumor assessments, pharmacokinetics, biomarkers and safety&#xD;
      evaluations (adverse events, laboratory tests, vital sign measurements, physical&#xD;
      examinations, Eastern Cooperative Oncology Group [ECOG] performance status) over the time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 7, 2017</start_date>
  <completion_date type="Anticipated">December 10, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From the date of randomization to active multiple myeloma (MM) or the date of death, whichever occurs first (up to approximately 8 years)</time_frame>
    <description>PFS is time from randomization to active MM according to International Myeloma Working Group (IMWG) criteria or death. Per IMWG criteria, active MM (SLiM-CRAB) is defined as: greater than or equal to (&gt;=)60 percent (%) bone marrow plasma cells (BMPCs), free light chain (FLC) involved/uninvolved ratio &gt;=100, greater than (&gt;)1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Biochemical or Diagnostic (SLiM-CRAB) Progression</measure>
    <time_frame>Up to biochemical or diagnostic progression (up to approximately 8 years)</time_frame>
    <description>Time to biochemical or diagnostic progression is defined as the earlier of time to biochemical progression or diagnostic (SLiM-CRAB) progression. SLiM-CRAB is defined as &gt;=60% bone marrow plasma cells, free light chain involved/uninvolved ratio &gt;=100, &gt;1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>ORR is defined as percentage of participants with partial response (PR) or better (very good partial response [VGPR], complete response [CR], and stringent complete response [sCR]) as defined by IMWG criteria. PR: &gt;=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by &gt;=90% 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 chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a &gt;=50% reduction in BMPC, with baseline BMPC percentage &gt;=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or &gt;=90% reduction in serum M-protein plus urine M-protein &lt;100 mg/24 hours. CR: negative immunofixation on serum and urine, and &lt;5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Response (CR) Rate</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>CR rate was defined as the percentage of participants with a CR (or better [sCR]) as defined by the IMWG response criteria. IMWG criteria for CR: negative immunofixation on serum and urine, and &lt;5% PCs in bone marrow. IMWG criteria for sCR: CR as defined above, plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First-Line Treatment for Multiple Myeloma (MM)</measure>
    <time_frame>Post-progressive disease (PD) follow-up, every 6 months until end of study (up to approximately 8 years)</time_frame>
    <description>Time to first-line treatment for MM was defined as the time from the date of randomization to the date of the first-line treatment given for MM (post disease progression).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival on First-Line Treatment for MM (PFS2)</measure>
    <time_frame>Post-PD follow-up, every 6 months until end of study (up to approximately 8 years)</time_frame>
    <description>PFS2 is time from date of randomization to date of documented PD on first line treatment given for MM or death, whichever comes first. IMWG criteria for PD: &gt;=25% from lowest response level in serum M-component (the absolute increase must be &gt;=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the 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 the difference between involved and uninvolved free light chain levels and the absolute increase must be &gt;10 mg/dL. BMPC%: the absolute % must be &gt;=10%; 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 or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Throughout study, and at least every 3 months until PD; post-PD, every 6 months until end of study (up to approximately 8 years)</time_frame>
    <description>OS was defined as the time from the date of randomization to the date of the participant's death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants who Progress to MM With Adverse Prognostic Features</measure>
    <time_frame>At screening and PD (up to approximately 8 years)</time_frame>
    <description>Adverse prognostic features includes International Staging System Stage III (based on beta2 [β2]-microglobulin &gt;=5.5 milligram per liter [mg/L] [median survival 29 months]) and adverse cytogenetic characteristics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Daratumumab Pharmacokinetic (PK) Concentration</measure>
    <time_frame>Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)</time_frame>
    <description>PK concentration of Daratumumab will be measured.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Daratumumab</measure>
    <time_frame>Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)</time_frame>
    <description>The Cmax is the maximum observed plasma concentration of Daratumumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Observed Concentration (Cmin) of Daratumumab</measure>
    <time_frame>Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)</time_frame>
    <description>The Cmin is the minimum observed plasma concentration of Daratumumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-daratumumab Antibodies</measure>
    <time_frame>Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)</time_frame>
    <description>Participant's serum samples will be collected and screened for antibodies binding to daratumumab using validated immunoassay methods for evaluation of potential immunogenicity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies</measure>
    <time_frame>Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)</time_frame>
    <description>Participant's plasma samples will be collected and screened for antibodies binding to rHuPH20 and will be assessed in confirmatory and titer assays as necessary for the rHuPH20 immunogenicity assessment.</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, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)</time_frame>
    <description>EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer participants. It is composed of 30 items, multiitem measure (28 items) and 2 single-item measures. For the multiple item measure, 4 point scale is used and the score for each item range from &quot;1 = not at all&quot; to &quot;4 = very much&quot;. Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which will be rated on a 7 point scale ranging from &quot;1 = very poor&quot; to &quot;7 = excellent&quot;. Lower scores indicate worsening. Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale</measure>
    <time_frame>Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)</time_frame>
    <description>EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. EORTC QLQ-MY20 includes two scales: disease symptoms (6 questions) and future perspective (3 questions). Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future; and higher score for the disease symptoms scale indicates higher level of symptomatology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire</measure>
    <time_frame>Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)</time_frame>
    <description>The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a &quot;thermometer&quot; visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>From the date of initial documentation of a response to the date of first documented evidence of PD (up to approximately 8 years)</time_frame>
    <description>Duration of response is defined as date of onset of first response (PR or better [VGPR, CR, sCR]) until date of disease progression or death. PR: &gt;=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by &gt;=90% or to &lt;200 mg/24 hours; if the serum and urine M-protein are not measurable, &gt;=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a &gt;=50% reduction in bone marrow PC, with baseline bone marrow PC percentage &gt;=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or &gt;=90% reduction in serum M-protein plus urine M-protein &lt;100 mg/24 hours. CR: negative immunofixation on serum and urine, and &lt;5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response</measure>
    <time_frame>Up to End of Treatment (up to approximately 39 cycles [each cycle of 28 days] or 36 months, whichever occurs first)</time_frame>
    <description>Time to response is defined as the time from randomization until onset of first response (PR or better [VGPR, CR, sCR]). PR: &gt;=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by &gt;=90% or to &lt;200 mg/24 hours; if the serum and urine M-protein are not measurable, &gt;=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a &gt;=50% reduction in bone marrow PC, with baseline bone marrow PC percentage &gt;=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or &gt;=90% reduction in serum M-protein plus urine M-protein &lt;100 mg/24 hours. CR: negative immunofixation on serum and urine, and &lt;5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">390</enrollment>
  <condition>Smoldering Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm A: Active Monitoring</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants randomized to active monitoring will receive no study medication, but will undergo the same disease evaluations at the same frequency as participants randomized to daratumumab.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Daratumumab SC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1800 milligram (mg) of daratumumab co-formulated with 2000 units per milliliter (U/mL) of recombinant human hyaluronidase (rHuPH20) by subcutaneous (SC) injection until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab SC: daratumumab + rHuPH20</intervention_name>
    <description>Participants will receive daratumumab SC injection (daratumumab 1800 mg + rHuPH20 [2000 U/mL]) once weekly for Cycles 1 and 2 (Days 1, 8, 15, and 22 of each week), every 2 weeks for Cycle 3 to Cycle 6 (Days 1 and 15), and thereafter every 4 weeks (Day 1) until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion. Each cycle is 28 days in duration.</description>
    <arm_group_label>Arm B: Daratumumab SC</arm_group_label>
    <other_name>JNJ-54767414</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma&#xD;
             Working Group [IMWG] criteria) for less than or equal to (&lt;=) 5 years with measurable&#xD;
             disease at the time of randomization, defined as serum M protein greater than or equal&#xD;
             to (&gt;=) 10 gram per liter (g/L) or urine M protein &gt;= 200 milligram per 24 hours&#xD;
             (mg/24 hours) or involved serum free light chain (FLC) &gt;=100 milligram per liter&#xD;
             (mg/L) and abnormal serum FLC ratio&#xD;
&#xD;
          -  Clonal bone marrow plasma cells (BMPCs) &gt;= 10 percentage (%); and at least 1 of the&#xD;
             following risk factors; Serum M protein &gt;= 30 g/L, immunoglobulin (Ig)A SMM,&#xD;
             immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes (only IgA, IgM,&#xD;
             and IgG should be considered in determination for immunoparesis; IgD and IgE are not&#xD;
             considered in this assessment), serum involved: uninvolved FLC ratio &gt;= 8 and less&#xD;
             than (&lt;) 100, or clonal BMPCs greater than (&gt;) 50% to &lt;60% with measurable disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1&#xD;
&#xD;
          -  Women of childbearing potential must commit to either abstain continuously from&#xD;
             heterosexual sexual intercourse or to use highly effective method of contraception&#xD;
&#xD;
          -  A woman of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             at screening within 14 days prior to randomization&#xD;
&#xD;
          -  During the study and for 3 months after receiving the last dose of daratumumab, a&#xD;
             woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted&#xD;
             reproduction&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Multiple myeloma (MM), requiring treatment, defined by any of the following:&#xD;
&#xD;
               1. Bone lesions (1 or more osteolytic lesions on low-dose whole body computed&#xD;
                  tomography [LDCT], positron-emission tomography with computed tomography [PET-CT]&#xD;
                  or CT). Participants who have benign/post-traumatic bone lesions visible on&#xD;
                  screening images as well as previous imaging, may be considered for inclusion.&#xD;
                  Details (diagnosis, location, duration) on benign/post-traumatic pre-existing&#xD;
                  bone lesions that can be seen on the screening images (example [eg.], old&#xD;
                  fractures) and were also present on previous imaging are to be reported in the&#xD;
                  case report form (CRF)&#xD;
&#xD;
               2. Hypercalcemia (serum calcium greater than [&gt;]0.25 millimoles per liter [mmol/L]&#xD;
                  [&gt;1 milligram per deciliter {mg/dL}] higher than upper limit of normal [ULN] or&#xD;
                  &gt;2.75 mmol/L [&gt;11 mg/dL]). Participants who have clinically stable hypercalcemia&#xD;
                  attributable to a disease other than multiple myeloma (eg, hyperparathyroidism)&#xD;
                  may be considered for inclusion after a case by case review by the medical&#xD;
                  monitor&#xD;
&#xD;
               3. Renal insufficiency, preferably determined by creatinine clearance less than&#xD;
                  (&lt;)40 milliliter per minute (mL/min) measured or estimated using the Modification&#xD;
                  of Diet in Renal Disease (MDRD), or serum creatinine &gt;177 micromole per liter&#xD;
                  (μmol/L). Participants who have clinically stable renal insufficiency&#xD;
                  attributable to a disease other than multiple myeloma (eg, glomerulonephritis)&#xD;
                  may be considered for inclusion after a case by case review by the medical&#xD;
                  monitor&#xD;
&#xD;
               4. Anemia, defined as hemoglobin &lt;10 gram per deciliter (g/dL) or &gt;2 g/dL below&#xD;
                  lower limit of normal or both; transfusion support or concurrent treatment with&#xD;
                  erythropoietin stimulating agents is not permitted. Participants who have&#xD;
                  clinically stable anemia attributable to a disease other than multiple myeloma&#xD;
                  (eg, thalassemia, vitamin B12 deficiency, iron deficiency) may be considered for&#xD;
                  inclusion after a case by case review by the medical monitor&#xD;
&#xD;
               5. Clonal BMPC percentage &gt;=60%&#xD;
&#xD;
               6. Serum FLC ratio (involved:uninvolved) &gt;=100 (the involved FLC must be &gt;=100 mg/L)&#xD;
&#xD;
               7. More than 1 focal lesion &gt;=5 millimeter (mm) in diameter by magnetic resonance&#xD;
                  imaging (MRI)&#xD;
&#xD;
          -  Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis&#xD;
&#xD;
          -  Exposure to any of the following:&#xD;
&#xD;
               1. Prior exposure to daratumumab or prior exposure to other anti-Cluster of&#xD;
                  Differentiation 38 (anti-CD38) therapies&#xD;
&#xD;
               2. Prior exposure to approved or investigational treatments for SMM or MM (including&#xD;
                  but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs],&#xD;
                  or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate and&#xD;
                  denosumab as indicated for osteoporosis is acceptable&#xD;
&#xD;
               3. Exposure to investigational drug (including investigational vaccines) or invasive&#xD;
                  investigational medical device for any indication within 4 weeks or 5 half-lives,&#xD;
                  whichever is longer, before Cycle 1, Day 1&#xD;
&#xD;
               4. Ongoing treatment with corticosteroids with a dose &gt;10 milligram (mg) prednisone&#xD;
                  or equivalent per day at the time of randomization; or &gt;280 mg cumulative&#xD;
                  prednisone dose or equivalent for any 4-week period in the year prior to&#xD;
                  randomization&#xD;
&#xD;
               5. Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab),&#xD;
                  immunomodulators (eg, abatacept, methotrexate, azathioprine, cyclosporine) or&#xD;
                  other treatments that are likely to interfere with the study procedures or&#xD;
                  results&#xD;
&#xD;
          -  Received treatment (chemotherapy, surgery, et cetera [etc]) for a malignancy (other&#xD;
             than SMM) within 3 years before the date of randomization (exceptions are squamous and&#xD;
             basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other&#xD;
             non-invasive lesion), which is considered cured with minimal risk of recurrence within&#xD;
             3 years&#xD;
&#xD;
          -  Medical or psychiatric condition or disease (for example, active systemic disease&#xD;
             [including presence of auto-antibodies], uncontrolled diabetes) that is likely to&#xD;
             interfere with the study procedures or results, or that in the opinion of the&#xD;
             investigator, would constitute a hazard for participating in this study&#xD;
&#xD;
          -  Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal&#xD;
             antibodies, hyaluronidase, or other human proteins, or their excipients, or known&#xD;
             sensitivity to mammalian-derived products (including dairy allergy)&#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>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Oncology Associates, PC - HAL</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research, Inc.</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Cancer Institute</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals &amp; Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Jefferson General Hospital</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215-5418</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Southern Nevada Healthcare</name>
      <address>
        <city>North Las Vegas</city>
        <state>Nevada</state>
        <zip>89086</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University Medical Center</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute, Carolinas HealthCare System</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OHSU/CHM</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology P.A.</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA North Texas Health Care System</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology P.A.</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>90805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Aleman</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1118AAT</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Italiano de Buenos Aires</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1199ABD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CEMIC Saavedra</name>
      <address>
        <city>Ciudad de Buenos Aires</city>
        <zip>1431</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Privado - Centro Medico de Cordoba</name>
      <address>
        <city>Cordoba</city>
        <zip>X5016KEH</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Italiano de La Plata</name>
      <address>
        <city>La Plata</city>
        <zip>B1900AXI</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanatorio Britanico de Rosario</name>
      <address>
        <city>Rosario</city>
        <zip>2000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Hospital</name>
      <address>
        <city>Heidelberg</city>
        <zip>3150 or 3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Calvary Mater Newcastle Hospital</name>
      <address>
        <city>Waratah</city>
        <zip>2298</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Perth Blood Institute</name>
      <address>
        <city>West Perth</city>
        <zip>6005</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Woodville</city>
        <zip>5011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZNA</name>
      <address>
        <city>Antwerpen</city>
        <zip>2060</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ St.-Jan Brugge-Oostende AV</name>
      <address>
        <city>Brugge</city>
        <zip>8000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZBrussel</name>
      <address>
        <city>Brussel</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virga Jessa Ziekenhuis</name>
      <address>
        <city>Hasselt</city>
        <zip>3500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Az Groeninge</name>
      <address>
        <city>Kortrijk</city>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN</name>
      <address>
        <city>Florianopolis</city>
        <zip>88034-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidade Federal de Goias - Hospital das Clinicas da UFG</name>
      <address>
        <city>Goiânia</city>
        <zip>74605-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Joinvilense de Hematologia e Oncologia Ltda-Centro de Hematologia e Oncologia</name>
      <address>
        <city>Joinville</city>
        <zip>89201-260</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90035-003</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>22775-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sao Rafael</name>
      <address>
        <city>Salvador</city>
        <zip>41235-190</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base</name>
      <address>
        <city>Sao Jose do Rio Preto</city>
        <zip>15090-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Ensino e Pesquisa São Lucas</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01236-030</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Sao Germano</name>
      <address>
        <city>São Paulo</city>
        <zip>01455-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Cruz</name>
      <address>
        <city>São Paulo</city>
        <zip>04122-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tom Baker Cancer Center, University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cross Cancer Institute</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lakeridge Health Oshawa</name>
      <address>
        <city>Oshawa</city>
        <state>Ontario</state>
        <zip>L1G-2B9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Hradec Kralove</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Ostrava</name>
      <address>
        <city>Ostrava</city>
        <zip>70852</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni</name>
      <address>
        <city>Plzen</city>
        <zip>323 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie</name>
      <address>
        <city>Praha 2</city>
        <zip>128 08</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus N.</city>
        <zip>8200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Odense Universitetshospital</name>
      <address>
        <city>Odense C</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ålborg Universitetshospital</name>
      <address>
        <city>Ålborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Limoges - Fédération Hépatologie</name>
      <address>
        <city>Limoges</city>
        <zip>87000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Hotel Dieu</name>
      <address>
        <city>Nantes cedex 01</city>
        <zip>44035</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Bordeaux - Hospital Haut-Leveque</name>
      <address>
        <city>Pessac cedex</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier Lyon-Sud</name>
      <address>
        <city>Pierre Benite cedex</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU De Poitiers</name>
      <address>
        <city>Poitiers</city>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>l'Hôpital Pontchaillou</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bretonneau</name>
      <address>
        <city>Tours Cedex 9</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helios Kliniken Berlin Buch Gmbh</name>
      <address>
        <city>Berlin</city>
        <zip>13125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Barbara-Klinik Hamm GmbH</name>
      <address>
        <city>Hamm</city>
        <zip>59073</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Heidelberg Medizinische Klinik V</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Klinik A</name>
      <address>
        <city>Muenster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexandra General Hospital of Athens</name>
      <address>
        <city>Athens Attica</city>
        <zip>115 28</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem, I. Belgyogyaszati Klinika</name>
      <address>
        <city>Budapest N/a</city>
        <zip>1083</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem I.Belgyogyaszati Klinika</name>
      <address>
        <city>Budapest</city>
        <zip>1088</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet, Szent László Telephely</name>
      <address>
        <city>Budapest</city>
        <zip>1097</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debreceni Egyetem Klinikai Kozpont</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haemek</name>
      <address>
        <city>Afula</city>
        <zip>18101</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barzilai Medical Center</name>
      <address>
        <city>Ashkelon</city>
        <zip>78741</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bnai Zion Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>31048</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carmel Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3436212</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3525408</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Galilee Medical Center</name>
      <address>
        <city>Nahariya</city>
        <zip>22100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petah-Tiqva</city>
        <zip>49100</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center</name>
      <address>
        <city>Ramat Gan</city>
        <zip>52621</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Center</name>
      <address>
        <city>Tel-Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Sant'Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Businco Cancer Hospital</name>
      <address>
        <city>Cagliari</city>
        <zip>09121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Santa Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <zip>12100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Eugenio</name>
      <address>
        <city>Roma</city>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Università di Roma 'La Sapienza' - Ospedale Umberto 1°</name>
      <address>
        <city>Roma</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. Città della Salute e della Scienza di Torino- Divisione di Ematologia</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST dei Sette Laghi, Ospedale di Circolo e Fonazione Macchi</name>
      <address>
        <city>Varese</city>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fukuoka University Hospital</name>
      <address>
        <city>Fukuoka</city>
        <zip>814-0180</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chugoku Central Hospital</name>
      <address>
        <city>Fukuyama</city>
        <zip>720-0001</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ogaki Municipal Hospital</name>
      <address>
        <city>Gifu</city>
        <zip>503-8502</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe City Medical Center General Hospital</name>
      <address>
        <city>Hyogo</city>
        <zip>650-0047</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kagoshima University Hospital</name>
      <address>
        <city>Kagoshima</city>
        <zip>890-8520</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanazawa University Hospital</name>
      <address>
        <city>Kanazawa</city>
        <zip>920-8641</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Osaka Minami Medical Center</name>
      <address>
        <city>Kawachi-Nagano</city>
        <zip>586-8521</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kumamoto Medical Center</name>
      <address>
        <city>Kumamoto-shi</city>
        <zip>860-0008</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kurume University Hospital</name>
      <address>
        <city>Kurume</city>
        <zip>830-0011</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyoto Kuramaguchi Medical Center</name>
      <address>
        <city>Kyoto</city>
        <zip>603-8151</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Matsumoto Medical Center</name>
      <address>
        <city>Matsumoto</city>
        <zip>399-8701</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Matsuyama Red Cross Hospital</name>
      <address>
        <city>Matsuyama</city>
        <zip>790-8524</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nagoya City University Hospital</name>
      <address>
        <city>Nagoya</city>
        <zip>467-8602</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Niigata Cancer Center Hospital</name>
      <address>
        <city>Niigata</city>
        <zip>951-8566</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Okayama Medical Center</name>
      <address>
        <city>Okayama</city>
        <zip>701-1192</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Sendai Medical Center</name>
      <address>
        <city>Sendai-City</city>
        <zip>983-8520</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Shibukawa Medical Center</name>
      <address>
        <city>Shibukawa</city>
        <zip>377-0280</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japanese Red Cross Medical Center</name>
      <address>
        <city>Shibuya</city>
        <zip>150-8935</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>iBiomed Research Unit</name>
      <address>
        <city>Aguascalientes</city>
        <zip>20121</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JM Research, SC</name>
      <address>
        <city>Cuernavaca</city>
        <zip>62290</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigación Farmacéutica Especializada</name>
      <address>
        <city>Guadalajara</city>
        <zip>44160</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Atención e Investigación Clínica en Oncología</name>
      <address>
        <city>Merida</city>
        <zip>97134</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Nuevo León</name>
      <address>
        <city>Monterrey</city>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gelre Ziekenhuis</name>
      <address>
        <city>Apeldoorn</city>
        <zip>7334 DZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haga ziekenhuis</name>
      <address>
        <city>Den Haag</city>
        <zip>2545 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Schweitzer Ziekenhuis</name>
      <address>
        <city>Dordrecht</city>
        <zip>3318 AT</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ETZ TweeSteden</name>
      <address>
        <city>Tilburg</city>
        <zip>5042 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital HF Ullevål sykehus</name>
      <address>
        <city>Oslo</city>
        <zip>0450</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza</name>
      <address>
        <city>Brzozow</city>
        <zip>36-200</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-168</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Specjalistyczny w Legnicy</name>
      <address>
        <city>Legnica</city>
        <zip>59-220</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Center sp. z o.o MEDIC-R s.k.</name>
      <address>
        <city>Poznań</city>
        <zip>60-848</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Hematologii i Transfuzjologii</name>
      <address>
        <city>Warszawa</city>
        <zip>02-776</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emergency Hospital of Dzerzhinsk</name>
      <address>
        <city>Dzerzhinsk</city>
        <zip>606019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City clinical hospital n.a. S.P.Botkin</name>
      <address>
        <city>Moscow</city>
        <zip>125284</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Hospital # 40</name>
      <address>
        <city>Moscow</city>
        <zip>129301</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nizhniy Novgorod Region Clinical Hospital</name>
      <address>
        <city>Nizhny Novgorod</city>
        <zip>603126</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Perm Medical Sanitary Unit#1</name>
      <address>
        <city>Perm</city>
        <zip>614078</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Hospital n.a.V.A.Baranov</name>
      <address>
        <city>Petrozavodsk</city>
        <zip>185019</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ryazan Regional Clinical Hospital</name>
      <address>
        <city>Ryazan</city>
        <zip>390003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Institute of Hematology and Transfusiology</name>
      <address>
        <city>St-Petersburg</city>
        <zip>191024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Dispensary of Komi Republic</name>
      <address>
        <city>Syktyvkar</city>
        <zip>167904</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Germans Trias I Pujol</name>
      <address>
        <city>Badalona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Clinic I Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Vall D Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>8035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Gral. Univ. Gregorio Maranon</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Infanta Leonor</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Ramon Y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Univ. de Navarra</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Quiron Madrid Pozuelo</name>
      <address>
        <city>Pozuelo De Alarcon, Madrid</city>
        <zip>28223</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Clinico Univ. de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Dr. Peset</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Falu Lasarett</name>
      <address>
        <city>Falun</city>
        <zip>79182</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunderby Sjukhus Medicinkliniken</name>
      <address>
        <city>Luelå</city>
        <zip>97180</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska Universitetssjukhuset Huddinge</name>
      <address>
        <city>Stockholm</city>
        <zip>141 86</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara Numune Egitim ve Arastirma Hastanesi</name>
      <address>
        <city>Ankara</city>
        <zip>06230</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara University Medical Faculty</name>
      <address>
        <city>Ankara</city>
        <zip>6100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Trakya University Hospital</name>
      <address>
        <city>Edirne</city>
        <zip>22030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Istanbul Medical Faculty</name>
      <address>
        <city>Istanbul</city>
        <zip>34093</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erciyes University Medical Faculty</name>
      <address>
        <city>Kayseri</city>
        <zip>38030</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>On Dokuz Mayis University Medical Faculty Department of Hematology</name>
      <address>
        <city>Samsun</city>
        <zip>55139</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heart of England NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B9 5SS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol NHS Trust</name>
      <address>
        <city>Bristol</city>
        <zip>BS2 8ED</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kent and Canterbury Hospital</name>
      <address>
        <city>Canterbury</city>
        <zip>CT1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Bartholomew's Hospital</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christie Hospital NHS Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <zip>NG5 1PB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Stoke University Hospital</name>
      <address>
        <city>Stoke-On-Trent</city>
        <zip>ST4 6QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Norway</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</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>
    <mesh_term>Smoldering Multiple Myeloma</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/NCT03301220
org study id: CR108172
secondary id: 54767414SMM3001
secondary id: 2016-001205-16
nct id: NCT03301220
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study is to determine whether treatment with daratumumab
      administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with
      active monitoring in participants with high-risk smoldering multiple myeloma (SMM).
This study consists of 3 phases: Screening Phase (up to 35 days), an Active Monitoring Phase
      or a Treatment Phase of 39 cycles or 36 months (whichever occurs first), and a Follow-up
      Phase which will continue until death, lost to follow-up, consent withdrawal, or study end
      (approximately 8 years after the first participant is randomized), whichever occurs first.
      Active monitoring cycles and treatment cycles are 4 weeks in length. For all participants,
      disease evaluations will be performed every 12 weeks until confirmed progressive disease
      (PD). After PD, survival is to be followed at least every 6 months, until the end of the
      study. Participants will undergo tumor assessments, pharmacokinetics, biomarkers and safety
      evaluations (adverse events, laboratory tests, vital sign measurements, physical
      examinations, Eastern Cooperative Oncology Group [ECOG] performance status) over the time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free Survival (PFS)
time frame: From the date of randomization to active multiple myeloma (MM) or the date of death, whichever occurs first (up to approximately 8 years)
description: PFS is time from randomization to active MM according to International Myeloma Working Group (IMWG) criteria or death. Per IMWG criteria, active MM (SLiM-CRAB) is defined as: greater than or equal to (>=)60 percent (%) bone marrow plasma cells (BMPCs), free light chain (FLC) involved/uninvolved ratio >=100, greater than (>)1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions.
measure: Time to Biochemical or Diagnostic (SLiM-CRAB) Progression
time frame: Up to biochemical or diagnostic progression (up to approximately 8 years)
description: Time to biochemical or diagnostic progression is defined as the earlier of time to biochemical progression or diagnostic (SLiM-CRAB) progression. SLiM-CRAB is defined as >=60% bone marrow plasma cells, free light chain involved/uninvolved ratio >=100, >1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions.
measure: Overall Response Rate (ORR)
time frame: Up to approximately 8 years
description: ORR is defined as percentage of participants with partial response (PR) or better (very good partial response [VGPR], complete response [CR], and stringent complete response [sCR]) as defined by IMWG criteria. PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% 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 chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a >=50% reduction in BMPC, with baseline BMPC percentage >=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.
measure: Complete Response (CR) Rate
time frame: Up to approximately 8 years
description: CR rate was defined as the percentage of participants with a CR (or better [sCR]) as defined by the IMWG response criteria. IMWG criteria for CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. IMWG criteria for sCR: CR as defined above, plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
measure: Time to First-Line Treatment for Multiple Myeloma (MM)
time frame: Post-progressive disease (PD) follow-up, every 6 months until end of study (up to approximately 8 years)
description: Time to first-line treatment for MM was defined as the time from the date of randomization to the date of the first-line treatment given for MM (post disease progression).
measure: Progression-Free Survival on First-Line Treatment for MM (PFS2)
time frame: Post-PD follow-up, every 6 months until end of study (up to approximately 8 years)
description: PFS2 is time from date of randomization to date of documented PD on first line treatment given for MM or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; 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 or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.
measure: Overall Survival (OS)
time frame: Throughout study, and at least every 3 months until PD; post-PD, every 6 months until end of study (up to approximately 8 years)
description: OS was defined as the time from the date of randomization to the date of the participant's death.
measure: Percentage of Participants who Progress to MM With Adverse Prognostic Features
time frame: At screening and PD (up to approximately 8 years)
description: Adverse prognostic features includes International Staging System Stage III (based on beta2 [β2]-microglobulin >=5.5 milligram per liter [mg/L] [median survival 29 months]) and adverse cytogenetic characteristics.
measure: Serum Daratumumab Pharmacokinetic (PK) Concentration
time frame: Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
description: PK concentration of Daratumumab will be measured.
measure: Maximum Observed Concentration (Cmax) of Daratumumab
time frame: Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
description: The Cmax is the maximum observed plasma concentration of Daratumumab.
measure: Minimum Observed Concentration (Cmin) of Daratumumab
time frame: Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
description: The Cmin is the minimum observed plasma concentration of Daratumumab.
measure: Number of Participants With Anti-daratumumab Antibodies
time frame: Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
description: Participant's serum samples will be collected and screened for antibodies binding to daratumumab using validated immunoassay methods for evaluation of potential immunogenicity.
measure: Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies
time frame: Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
description: Participant's plasma samples will be collected and screened for antibodies binding to rHuPH20 and will be assessed in confirmatory and titer assays as necessary for the rHuPH20 immunogenicity assessment.
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
time frame: Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)
description: EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer participants. It is composed of 30 items, multiitem measure (28 items) and 2 single-item measures. For the multiple item measure, 4 point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which will be rated on a 7 point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening. Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning
measure: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale
time frame: Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)
description: EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. EORTC QLQ-MY20 includes two scales: disease symptoms (6 questions) and future perspective (3 questions). Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future; and higher score for the disease symptoms scale indicates higher level of symptomatology.
measure: Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire
time frame: Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)
description: The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).
measure: Duration of Response
time frame: From the date of initial documentation of a response to the date of first documented evidence of PD (up to approximately 8 years)
description: Duration of response is defined as date of onset of first response (PR or better [VGPR, CR, sCR]) until date of disease progression or death. PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a >=50% reduction in bone marrow PC, with baseline bone marrow PC percentage >=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
measure: Time to Response
time frame: Up to End of Treatment (up to approximately 39 cycles [each cycle of 28 days] or 36 months, whichever occurs first)
description: Time to response is defined as the time from randomization until onset of first response (PR or better [VGPR, CR, sCR]). PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a >=50% reduction in bone marrow PC, with baseline bone marrow PC percentage >=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
arm group label: Arm A: Active Monitoring
arm group type: No Intervention
description: Participants randomized to active monitoring will receive no study medication, but will undergo the same disease evaluations at the same frequency as participants randomized to daratumumab.
arm group label: Arm B: Daratumumab SC
arm group type: Experimental
description: Participants will receive 1800 milligram (mg) of daratumumab co-formulated with 2000 units per milliliter (U/mL) of recombinant human hyaluronidase (rHuPH20) by subcutaneous (SC) injection until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion.
intervention type: Drug
intervention name: Daratumumab SC: daratumumab + rHuPH20
description: Participants will receive daratumumab SC injection (daratumumab 1800 mg + rHuPH20 [2000 U/mL]) once weekly for Cycles 1 and 2 (Days 1, 8, 15, and 22 of each week), every 2 weeks for Cycle 3 to Cycle 6 (Days 1 and 15), and thereafter every 4 weeks (Day 1) until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion. Each cycle is 28 days in duration.
arm group label: Arm B: Daratumumab SC
other name: JNJ-54767414
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
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country: Argentina
country: Australia
country: Belgium
country: Brazil
country: Canada
country: Czechia
country: Denmark
country: France
country: Germany
country: Greece
country: Hungary
country: Israel
country: Italy
country: Japan
country: Mexico
country: Netherlands
country: Norway
country: Poland
country: Russian Federation
country: Spain
country: Sweden
country: Turkey
country: United Kingdom
country: United States
country: China
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Smoldering Multiple Myeloma
mesh term: Daratumumab