<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/NCT01711671</url>
  </required_header>
  <id_info>
    <org_study_id>DEK-DKK1-P101</org_study_id>
    <secondary_id>DKN-01</secondary_id>
    <secondary_id>LY2812176</secondary_id>
    <nct_id>NCT01711671</nct_id>
  </id_info>
  <brief_title>A Study of DKN-01 and Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>A Pilot Study of DKN-01 and Lenalidomide (Revlimid®)/Dexamethasone Versus Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Leap Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Leap Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A study to evaluate the safety, efficacy and bone changes with combination therapy of&#xD;
      intravenous (IV) infused DKN-01 and lenalidomide/dexamethasone, versus lenalidomide and&#xD;
      dexamethasone in relapsed or refractory multiple myeloma (MM) patients&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>Phase 1</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>Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) standard uptake value (SUV)</measure>
    <time_frame>Pre-study to after 6 months of therapy</time_frame>
    <description>SUV as measured by NaF-PET/CT in both myeloma bone lesions and normal bone</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) influx constant (Ki)</measure>
    <time_frame>Pre-study to after 6 months of therapy</time_frame>
    <description>Ki as measured by NaF-PET/CT in both myeloma bone lesions and normal bone</description>
  </primary_outcome>
  <primary_outcome>
    <measure>F18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) standard uptake value (SUV)</measure>
    <time_frame>Pre-study to after 6 months of therapy</time_frame>
    <description>SUV as measured by FDG-PET/CT in both myeloma bone lesions and normal bone</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with treatment emergent adverse events</measure>
    <time_frame>Baseline to study completion (approximately 7 months)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>Baseline to study completion (approximately 7 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Baseline to study completion (approximately 7 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Baseline to study completion (approximately 7 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Baseline to study completion (approximately 7 months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: area under the concentration - time curve (AUC) of a single dose of DKN-01</measure>
    <time_frame>Dosing interval of 2 weeks following the first dose in Cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: maximum plasma concentration (Cmax) of a single dose of DKN-01</measure>
    <time_frame>Dosing interval of 2 weeks following the first dose in Cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics: trough DKN-01 concentrations on Cycle 2 and Cycle 3</measure>
    <time_frame>Cycle 2 Day 1 Pre-dose, Cycle 3 Day 1 Pre-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>DKN-01 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DKN-01 plus lenalidomide (Revlimid)/dexamethasone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DKN-01 600mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DKN-01 plus lenalidomide (Revlimid)/dexamethasone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lenalidomide (Revlimid)/dexamethasone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DKN-01 300 mg</intervention_name>
    <description>300 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone</description>
    <arm_group_label>DKN-01 300mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DKN-01 600 mg</intervention_name>
    <description>600 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone</description>
    <arm_group_label>DKN-01 600mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Current approved standard of care</description>
    <arm_group_label>Standard of Care</arm_group_label>
    <other_name>Lenalidomide</other_name>
    <other_name>Revlimid</other_name>
    <other_name>Dexamethasone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Relapsed or refractory Multiple Myeloma (MM)&#xD;
&#xD;
             a. Treated with at least 1 prior regimen for myeloma&#xD;
&#xD;
               1. Prior treatment with bortezomib (Velcade) is acceptable with a wash-out of 2&#xD;
                  weeks&#xD;
&#xD;
               2. Treatment with prior autologous transplant is permitted&#xD;
&#xD;
               3. If a transplant is used as consolidation following chemotherapy, without&#xD;
                  intervening disease progression, it will be considered 1 line of treatment with&#xD;
                  the preceding chemotherapy&#xD;
&#xD;
          -  Diagnosis of symptomatic MM as defined by the International Myeloma Working Group&#xD;
             (IMWG) :&#xD;
&#xD;
               1. Second line or greater/Refractory/Relapsed, Stage I, Stage II, Stage III&#xD;
&#xD;
               2. Measureable disease as indicated by monoclonal protein in the serum of greater&#xD;
                  than or equal to (≥) 1 grams per deciliter (g/dL), involved serum free light&#xD;
                  chain assay ≥10 mg/dL (≥100 mg/L) provided the serum free light chain ratio is&#xD;
                  abnormal; monoclonal light chain in the urine protein electrophoresis of ≥ 200&#xD;
                  mg/24 hours, or measurable plasmacytoma&#xD;
&#xD;
          -  At least 1 osteolytic bone lesion&#xD;
&#xD;
          -  Disease-free of active second/secondary or prior malignancies for equal to or over 5&#xD;
             years with the exception of currently treated basal cell, squamous cell carcinoma of&#xD;
             the skin, or carcinoma &quot;in-situ&quot; of the cervix or breast&#xD;
&#xD;
          -  Ambulatory patients greater than or equal to (≥) 30 years of age&#xD;
&#xD;
          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale&#xD;
&#xD;
          -  Estimated life expectancy of ≥ 26 weeks&#xD;
&#xD;
          -  Adequate organ function including:&#xD;
&#xD;
               1. Hematologic:&#xD;
&#xD;
                    1. Absolute neutrophil count (ANC) greater than or equal to (≥) 1000/microliter&#xD;
&#xD;
                    2. Platelet (PLT) count ≥ 75,000/microliter&#xD;
&#xD;
                    3. Hemoglobin (Hgb) ≥ 8.0 g/dL&#xD;
&#xD;
               2. Acceptable coagulation status:&#xD;
&#xD;
                    1. Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.2 x the&#xD;
                       upper limit of normal (ULN) unless receiving anticoagulation therapy. If&#xD;
                       receiving anticoagulation therapy, eligibility will be based upon&#xD;
                       International Normalization Ratio (INR)&#xD;
&#xD;
                    2. International normalized ratio (INR) less than or equal to (≤) 1.6 (unless&#xD;
                       receiving anticoagulation therapy)&#xD;
&#xD;
                         -  If receiving warfarin: INR ≤ 3.0 (and no active bleeding, [i.e., no&#xD;
                            bleeding within 14 days prior to first dose of study therapy])&#xD;
&#xD;
               3. Hepatic:&#xD;
&#xD;
                    1. Bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
                    2. Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 2.5 x ULN (if&#xD;
                       liver metastases are present, then ≤ 5 x ULN is allowed)&#xD;
&#xD;
               4. Renal:&#xD;
&#xD;
                    1. Calculated creatinine clearance ≥ 45 mL using the Cockcroft and Gault Method&#xD;
&#xD;
          -  Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy&#xD;
             test within 10 to 14 days and again within 24 hours of starting study drug&#xD;
&#xD;
               1. WCBP must agree to have pregnancy tests monthly (every 14 days for women with&#xD;
                  irregular cycles) while on study drug and 4 weeks after the last dose of study&#xD;
                  drug&#xD;
&#xD;
               2. Men must also agree to use a condom if their partner is of child bearing&#xD;
                  potential, even if they have had a successful vasectomy&#xD;
&#xD;
               3. Males and females with reproductive potential must agree to use medically&#xD;
                  approved contraceptive precautions starting 4 weeks prior to initiation of the&#xD;
                  therapy and during the trial and for 18 months following the last dose of study&#xD;
                  drug&#xD;
&#xD;
               4. Should a woman become pregnant or suspect she is pregnant while participating in&#xD;
                  this study, she should inform her treating physician immediately&#xD;
&#xD;
          -  Provide written informed consent prior to any study-specific procedures&#xD;
&#xD;
          -  Are reliable and willing to make themselves available for the duration of the study&#xD;
             and are willing to follow study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received treatment with an investigational drug, which has not received regulatory&#xD;
             approval for any indication, within 28 days of study treatment with DKN-01&#xD;
&#xD;
          -  Received any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell&#xD;
             infusions) within 56 days of entry&#xD;
&#xD;
          -  Previously treated with an anti-Dickkopf-1 (anti-DKK-1) or antibody therapy, or have&#xD;
             had a significant allergy to a known pharmaceutical therapy that, in the opinion of&#xD;
             the Investigator, poses an increased risk to the patient&#xD;
&#xD;
          -  Received radiation therapy, surgery, or chemotherapy within 2 weeks prior to study&#xD;
             entry (6 weeks for nitrosoureas or Mitomycin C)&#xD;
&#xD;
          -  Received bisphosphonates (e.g., etidronate, clodronate, tiludronate, pamidronate,&#xD;
             neridronate, olpadronate, alendronate, ibandronate, risedronate, zoledronate) within 2&#xD;
             weeks prior to study entry&#xD;
&#xD;
          -  Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with&#xD;
             treated CNS metastases are eligible provided their disease is radiographically stable,&#xD;
             asymptomatic, and they are not currently receiving corticosteroids and/or&#xD;
             anticonvulsants. Screening of asymptomatic patients without a history of CNS&#xD;
             metastases is not required&#xD;
&#xD;
          -  Have a history of major organ transplant (for example: heart, lungs, liver, and&#xD;
             kidney)&#xD;
&#xD;
          -  Are pregnant or nursing&#xD;
&#xD;
          -  Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface&#xD;
             antigen (HBSAg), or hepatitis C antibodies (HCAb)&#xD;
&#xD;
          -  Active, uncontrolled bacterial, viral, or fungal infections, including urinary tract&#xD;
             infection, within 7 days of study entry requiring systemic therapy&#xD;
&#xD;
          -  Serious cardiac condition such as myocardial infarction within the past 6 months,&#xD;
             unstable angina, or Class III or IV congestive heart failure as defined by the New&#xD;
             York Heart Association (NYHA); have ECG abnormalities including baseline 12-lead ECG&#xD;
             with Fridericia-corrected QT interval (QTcF) &gt; 470 msec (female) or &gt; 450 msec (male),&#xD;
             a history of congenital long QT syndrome, or any ECG abnormality that, in the opinion&#xD;
             of the Investigator, would preclude safe participation in the study&#xD;
&#xD;
          -  History of osteonecrosis of the hip or have evidence of structural bone abnormalities&#xD;
             in the proximal femur on MRI scan that are considered clinically significant or may&#xD;
             have an impact on the interpretation of the scan. Degenerative changes of the hip&#xD;
             joint are not exclusionary&#xD;
&#xD;
          -  Known concomitant disease(s) known to influence calcium metabolism including&#xD;
             hyperparathyroidism, hyperthyroidism, Paget's disease of bone, or any other concurrent&#xD;
             severe or uncontrolled concomitant medical condition that, in the opinion of the&#xD;
             Investigator, would preclude participation in this study&#xD;
&#xD;
          -  Patients who are currently receiving lithium chloride (LiCl)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Whitlock</last_name>
    <role>Study Director</role>
    <affiliation>Theorem Clinical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>October 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>March 8, 2017</last_update_submitted>
  <last_update_submitted_qc>March 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2017</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>Dexamethasone</mesh_term>
    <mesh_term>Lenalidomide</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/NCT01711671
org study id: DEK-DKK1-P101
secondary id: DKN-01
secondary id: LY2812176
nct id: NCT01711671
lead sponsor: 
has dmc: No
A study to evaluate the safety, efficacy and bone changes with combination therapy of
      intravenous (IV) infused DKN-01 and lenalidomide/dexamethasone, versus lenalidomide and
      dexamethasone in relapsed or refractory multiple myeloma (MM) patients
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) standard uptake value (SUV)
time frame: Pre-study to after 6 months of therapy
description: SUV as measured by NaF-PET/CT in both myeloma bone lesions and normal bone
measure: Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) influx constant (Ki)
time frame: Pre-study to after 6 months of therapy
description: Ki as measured by NaF-PET/CT in both myeloma bone lesions and normal bone
measure: F18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) standard uptake value (SUV)
time frame: Pre-study to after 6 months of therapy
description: SUV as measured by FDG-PET/CT in both myeloma bone lesions and normal bone
measure: Number of patients with treatment emergent adverse events
time frame: Baseline to study completion (approximately 7 months)
measure: Overall response rate (ORR)
time frame: Baseline to study completion (approximately 7 months)
measure: Progression free survival (PFS)
time frame: Baseline to study completion (approximately 7 months)
measure: Duration of response
time frame: Baseline to study completion (approximately 7 months)
measure: Overall survival
time frame: Baseline to study completion (approximately 7 months)
measure: Pharmacokinetics: area under the concentration - time curve (AUC) of a single dose of DKN-01
time frame: Dosing interval of 2 weeks following the first dose in Cycle 1
measure: Pharmacokinetics: maximum plasma concentration (Cmax) of a single dose of DKN-01
time frame: Dosing interval of 2 weeks following the first dose in Cycle 1
measure: Pharmacokinetics: trough DKN-01 concentrations on Cycle 2 and Cycle 3
time frame: Cycle 2 Day 1 Pre-dose, Cycle 3 Day 1 Pre-dose
arm group label: DKN-01 300mg
arm group type: Experimental
description: DKN-01 plus lenalidomide (Revlimid)/dexamethasone
arm group label: DKN-01 600mg
arm group type: Experimental
description: DKN-01 plus lenalidomide (Revlimid)/dexamethasone
arm group label: Standard of Care
arm group type: Active Comparator
description: Lenalidomide (Revlimid)/dexamethasone
intervention type: Drug
intervention name: DKN-01 300 mg
description: 300 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone
arm group label: DKN-01 300mg
intervention type: Drug
intervention name: DKN-01 600 mg
description: 600 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone
arm group label: DKN-01 600mg
intervention type: Drug
intervention name: Standard of Care
description: Current approved standard of care
arm group label: Standard of Care
other name: Lenalidomide
other name: Revlimid
other name: Dexamethasone
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Paul Whitlock
role: Study Director
affiliation: Theorem Clinical Research
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Lenalidomide