<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/NCT03809780</url>
  </required_header>
  <id_info>
    <org_study_id>LENDER</org_study_id>
    <nct_id>NCT03809780</nct_id>
  </id_info>
  <brief_title>Study to Demonstrate Clinical Benefit of Lenalidomide and Dexamethasone</brief_title>
  <acronym>LENDER</acronym>
  <official_title>Multicenter Phase II Study to Demonstrate Clinical Benefit of Lenalidomide and Dexamethasone in Elderly Unfit Patients With Newly Diagnosed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kosin University Gospel Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Kosin University Gospel Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Recent prospective multicenter phase II study assessed the efficacy and tolerability of lower&#xD;
      dose lenalidomide (15mg) and dexamethasone (20mg) in frail patients with relapsed or&#xD;
      refractory MM. The overall response rate was 71% including complete remission of 15%. Median&#xD;
      progression free survival and overall survival were 8.9 and 30.5 months. In addition, grade&#xD;
      3-4 toxicities such as neutropenia, and infections were reduced. This study supported that&#xD;
      lower dose lenalidomide may be optimal stating dose for elderly patients with frailty.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multiple myeloma (MM) is a malignant plasma cell disorder that occurs mainly in older adults.&#xD;
      The median age at diagnosis is approximately 70 years, and two-thirds of patients with newly&#xD;
      diagnosed MM are older than 65years. As life expectancy increases, the population of older&#xD;
      individuals grows. Consequently, the number of patients with MM, especially elderly patients,&#xD;
      is expected to increase considerably in the next two decades. Elderly patients may have a&#xD;
      variety of comorbidities and reduced physical function at diagnosis, and may be intolerable&#xD;
      to standard chemotherapy.&#xD;
&#xD;
      Recent prospective multicenter phase II study assessed the efficacy and tolerability of lower&#xD;
      dose lenalidomide (15mg) and dexamethasone (20mg) in frail patients with relapsed or&#xD;
      refractory MM[8]. The overall response rate was 71% including complete remission of 15%.&#xD;
      Median progression free survival and overall survival were 8.9 and 30.5 months. In addition,&#xD;
      grade 3-4 toxicities such as neutropenia, and infections were reduced. This study supported&#xD;
      that lower dose lenalidomide may be optimal stating dose for elderly patients with frailty.&#xD;
&#xD;
      Therefore, investigators thought that the use of lower dose of lenalidomide in the frail&#xD;
      group is expected to increase the effectiveness as it is used for a long time while reducing&#xD;
      toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 11, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Elderly unfit patients with newly diagnosed multiple myeloma</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2 years Progression Free Survival rates</measure>
    <time_frame>2year</time_frame>
    <description>To evaluate the progression free survival rates at 2 years</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>2 years Event-free survival rates</measure>
    <time_frame>2year</time_frame>
    <description>To evaluate the event free survival rates at 2 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2 years Overall Survival rates</measure>
    <time_frame>2year</time_frame>
    <description>To evaluate the overall survival rates at 2 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rates</measure>
    <time_frame>assessed for approximately 2 years after administration</time_frame>
    <description>To evaluated the overall response rates, defined as more than partial response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events by CTCAE</measure>
    <time_frame>assessed for approximately 2 years after administration</time_frame>
    <description>To assess the incidence of lenalidomide plus dexamethasone therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Optimal dose in frail patients</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>To assess the optimal dose of lenalidomide for frail patients with newly diagnosed multiple myeloma.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Lenalidomide,dexamethasone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose for intermediate risk group: lenalidomide 25mg day 1-21 plus dexamethasone 20mg weekly, every 4 weeks&#xD;
Low dose for high risk group: lenalidomide 15mg day 1-21 plus dexamethasone 10mg weekly, every 4 weeks Schedule</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>-high dose: [lenalidomide 25mg day 1-21 plus dexamethasone 20mg weekly] -Low dose: [lenalidomide 15mg day 1-21 plus dexamethasone 10mg weekly]</description>
    <arm_group_label>Lenalidomide,dexamethasone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>-high dose: [lenalidomide 25mg day 1-21 plus dexamethasone 20mg weekly] -Low dose: [lenalidomide 15mg day 1-21 plus dexamethasone 10mg weekly]</description>
    <arm_group_label>Lenalidomide,dexamethasone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients ≥ 70 years unfit and ineligible transplantation in patients with newly&#xD;
             diagnosed MM.&#xD;
&#xD;
          2. Patient is, in the investigator(s) opinion, willing and able to comply with the&#xD;
             protocol requirements.&#xD;
&#xD;
          3. Patient has given voluntary written informed consent before performance of any&#xD;
             study-related procedure not part of normal medical care, with the understanding that&#xD;
             consent may be withdrawn by the patient at any time without prejudice to their future&#xD;
             medical care.&#xD;
&#xD;
          4. Symptomatic MM based on standard CRAB criteria.&#xD;
&#xD;
          5. Patient has measurable disease, defined as follows:&#xD;
&#xD;
               -  any quantifiable serum monoclonal protein value (generally, but not necessarily,&#xD;
                  ≥ 0.5 g/dL of M-protein) and, where applicable,&#xD;
&#xD;
               -  urine light-chain excretion of &gt;200 mg/24 hours. For patients with oligo or&#xD;
                  non-secretory MM, it is required that they have&#xD;
&#xD;
               -  Measurable plasmacytoma &gt; 2 cm as determined by clinical examination or&#xD;
                  applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio&#xD;
                  (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this&#xD;
                  study will be oligo- or non-secretory MM with free light chains only in order to&#xD;
                  maximize interpretation of benefit results.&#xD;
&#xD;
          6. The frailty of the patient will be calculated by R-MCI and scoring according to renal&#xD;
             function, pulmonary function, activity, frailty, age, and cytogenetics, 0-3 points are&#xD;
             low risk (fit) risk (inadequate) and 7 or higher will be classified as high risk&#xD;
             (frail). Only inadequate and frail can be included.&#xD;
&#xD;
          7. Patients must meet the following clinical laboratory criteria with 21 days of starting&#xD;
             treatment:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet ≥ 50,000/mm3 (≥&#xD;
                  30,000/mm3 if myeloma involvement in the bone marrow is &gt;50%)&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). Alanine&#xD;
                  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.&#xD;
&#xD;
               -  Calculated creatinine clearance ≥ 30mL/min or creatinine &lt; 3mg/dL.&#xD;
&#xD;
          8. Patients who are planned to receive lenalidomide according to license of lenalidomide&#xD;
             and must be registered the Risk Management Program(Pregnancy Prevention Program) of&#xD;
             each company.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating females.&#xD;
&#xD;
          2. Male patients not agreeing to use an acceptable method for contraception (i.e., condom&#xD;
             or abstinence) for the duration of the study.&#xD;
&#xD;
          3. Females of childbearing potential not agreeing to use two acceptable methods for&#xD;
             contraception (e.g. a hormonal contraceptive, intrauterine device, diaphragm with&#xD;
             spermicide, condom with spermicide, or abstinence) for the duration of the study.&#xD;
&#xD;
          4. Previous treatment with anti-myeloma therapy (does not include radiotherapy,&#xD;
             bisphosphonates, or a single short course of steroid &lt; to the equivalent of&#xD;
             dexamethasone 40 mg/day for 4 days).&#xD;
&#xD;
          5. Any significant medical disease or conditions that, in the investigator's opinion, may&#xD;
             interfere with protocol adherence or subject's ability to give informed consent or&#xD;
             could place the subject at unacceptable risk.&#xD;
&#xD;
          6. Presence of clinical active infectious hepatitis type B or C, classified into&#xD;
             Child-Pugh class C (see Appendix V) and HIV.&#xD;
&#xD;
          7. Presence of acute active infection requiring antibiotics or infiltrative pulmonary&#xD;
             disease.&#xD;
&#xD;
          8. Contraindication to any of the required drugs or supportive treatments.&#xD;
&#xD;
          9. prior history of malignancies, other than MM, unless the subject had been free of&#xD;
             disease for &gt;= 3 years with the following exceptions: Basal cell CA of skin, Squamous&#xD;
             cell CA of skin, CA in situ of cervix and breast, incidental histologic finding of&#xD;
             prostate cancer (TNM stage of T1a or T1b)&#xD;
&#xD;
         10. Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
             various formulations.&#xD;
&#xD;
         11. Subjects with unstable cardiac disease: MI within 6 months before study participation,&#xD;
             NYHA heart failure class III-IV, uncontrolled hypertension/atrial fibrillation,&#xD;
&#xD;
         12. Conditions requiring chronic steroid/immunosuppressive therapy such as RA, MS, lupus,&#xD;
             that likely need additional steroid/IS treatment in addition to study treatment&#xD;
&#xD;
         13. Grade &gt;=2 Peripheral neuropathy&#xD;
&#xD;
         14. Subjects who are unwilling or unable to undergo antithrombotic therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>70 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ho Sup Lee, MD, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kosin University Gospel Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kosin University Gospel Hospital</name>
      <address>
        <city>Busan</city>
        <state>Western</state>
        <zip>49267</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>June 18, 2023</last_update_submitted>
  <last_update_submitted_qc>June 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kosin University Gospel Hospital</investigator_affiliation>
    <investigator_full_name>Ho Sup Lee</investigator_full_name>
    <investigator_title>MD, PhD. professor. Division of hematology-Oncology</investigator_title>
  </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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03809780
org study id: LENDER
nct id: NCT03809780
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Recent prospective multicenter phase II study assessed the efficacy and tolerability of lower
      dose lenalidomide (15mg) and dexamethasone (20mg) in frail patients with relapsed or
      refractory MM. The overall response rate was 71% including complete remission of 15%. Median
      progression free survival and overall survival were 8.9 and 30.5 months. In addition, grade
      3-4 toxicities such as neutropenia, and infections were reduced. This study supported that
      lower dose lenalidomide may be optimal stating dose for elderly patients with frailty.
Multiple myeloma (MM) is a malignant plasma cell disorder that occurs mainly in older adults.
      The median age at diagnosis is approximately 70 years, and two-thirds of patients with newly
      diagnosed MM are older than 65years. As life expectancy increases, the population of older
      individuals grows. Consequently, the number of patients with MM, especially elderly patients,
      is expected to increase considerably in the next two decades. Elderly patients may have a
      variety of comorbidities and reduced physical function at diagnosis, and may be intolerable
      to standard chemotherapy.

      Recent prospective multicenter phase II study assessed the efficacy and tolerability of lower
      dose lenalidomide (15mg) and dexamethasone (20mg) in frail patients with relapsed or
      refractory MM[8]. The overall response rate was 71% including complete remission of 15%.
      Median progression free survival and overall survival were 8.9 and 30.5 months. In addition,
      grade 3-4 toxicities such as neutropenia, and infections were reduced. This study supported
      that lower dose lenalidomide may be optimal stating dose for elderly patients with frailty.

      Therefore, investigators thought that the use of lower dose of lenalidomide in the frail
      group is expected to increase the effectiveness as it is used for a long time while reducing
      toxicity.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Elderly unfit patients with newly diagnosed multiple myeloma
primary purpose: Treatment
masking: None (Open Label)
measure: 2 years Progression Free Survival rates
time frame: 2year
description: To evaluate the progression free survival rates at 2 years
measure: 2 years Event-free survival rates
time frame: 2year
description: To evaluate the event free survival rates at 2 years
measure: 2 years Overall Survival rates
time frame: 2year
description: To evaluate the overall survival rates at 2 years
measure: Overall response rates
time frame: assessed for approximately 2 years after administration
description: To evaluated the overall response rates, defined as more than partial response.
measure: Incidence of Treatment-Emergent Adverse Events by CTCAE
time frame: assessed for approximately 2 years after administration
description: To assess the incidence of lenalidomide plus dexamethasone therapy
measure: Optimal dose in frail patients
time frame: through study completion, an average of 1 year
description: To assess the optimal dose of lenalidomide for frail patients with newly diagnosed multiple myeloma.
arm group label: Lenalidomide,dexamethasone
arm group type: Experimental
description: High dose for intermediate risk group: lenalidomide 25mg day 1-21 plus dexamethasone 20mg weekly, every 4 weeks
Low dose for high risk group: lenalidomide 15mg day 1-21 plus dexamethasone 10mg weekly, every 4 weeks Schedule
intervention type: Drug
intervention name: Lenalidomide
description: -high dose: [lenalidomide 25mg day 1-21 plus dexamethasone 20mg weekly] -Low dose: [lenalidomide 15mg day 1-21 plus dexamethasone 10mg weekly]
arm group label: Lenalidomide,dexamethasone
intervention type: Drug
intervention name: Dexamethasone
description: -high dose: [lenalidomide 25mg day 1-21 plus dexamethasone 20mg weekly] -Low dose: [lenalidomide 15mg day 1-21 plus dexamethasone 10mg weekly]
arm group label: Lenalidomide,dexamethasone
criteria: 
gender: All
minimum age: 70 Years
maximum age: N/A
healthy volunteers: No
last name: Ho Sup Lee, MD, PhD.
role: Principal Investigator
affiliation: Kosin University Gospel Hospital
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Kosin University Gospel Hospital
investigator full name: Ho Sup Lee
investigator title: MD, PhD. professor. Division of hematology-Oncology
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Lenalidomide
sharing ipd: Undecided