<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/NCT03815279</url>
  </required_header>
  <id_info>
    <org_study_id>LSH-17-001</org_study_id>
    <nct_id>NCT03815279</nct_id>
  </id_info>
  <brief_title>A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM)</brief_title>
  <acronym>iStopMM</acronym>
  <official_title>Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM): A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Landspitali University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Iceland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Landspitali University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the efficacy of treating patients with intermediate&#xD;
      risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and&#xD;
      lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and&#xD;
      carfilzomib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open label, single center, phase II study assessing the efficacy of treating&#xD;
      patients with intermediate-risk smoldering myeloma (SMM) with combinational therapy with&#xD;
      dexamethasone and lenalidomide and treating patients with high risk SMM and active multiple&#xD;
      myeloma (MM) with combinational therapy with dexamethasone, lenalidomide and carfilzomib.&#xD;
      Patients that are eligible for this study are participants in the IstopMM study&#xD;
      (ClinicalTrials.gov number, NCT03327597) that are diagnosed with intermediate or high-risk&#xD;
      SMM or active MM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">June 24, 2019</start_date>
  <completion_date type="Anticipated">January 2028</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>An investigator initiated, academic, non-randomized, open-label phase 2 study that will assess carfilzomib, lenalidomide and dexamethasone regimen as treatment in patients with intermediate-risk (not carfilzomib) or high-risk SMM or active MM.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of MRD negativity</measure>
    <time_frame>36 months after study enrollment</time_frame>
    <description>Minimal residual disease (MRD) as determined VDJ sequencing</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Up until 3 years after treatment</time_frame>
    <description>Rates of progression free survival with progression being determined by IMWG response criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up until 3 years after treatment</time_frame>
    <description>Overall survival as determened by the Icelandic National Cause of Death Registry</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Multiple Myeloma</condition>
  <condition>Smoldering Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>High-risk SMM and MM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twelve cycles of Carfilzomib-Lenalidomide-Dexamethason. Each cycle is 28 days. Carfilzomib intravenous, days 1, 8 and 15 (starting dose, 20 mg/m2 on day 1 of cycle 1; target dose, 56 mg/m2 thereafter) during cycles 1 through 12.&#xD;
Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks then 20 mg weekly for 16 weeks and thereafter 10 mg weekly for 16 weeks.&#xD;
Maintenance (1 year):&#xD;
Carfilzomib intravenous days 1 and 15 (56 mg/m2) during cycles 13 through 24. Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks Dexamethasone 10 mg weekly for 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intermediate-risk SMM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks, then 20 mg weekly for 16 weeks.&#xD;
Maintenance (1 year):&#xD;
Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Carfilzomib will be administered intravenously three times per cycle (28 day cycles) for cycle 1-12. Thereafter twice per cycle for cycle 13-24</description>
    <arm_group_label>High-risk SMM and MM</arm_group_label>
    <other_name>Kyprolis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Lenalidomide PO once daily on days 1-21 of a 28 day cycle</description>
    <arm_group_label>High-risk SMM and MM</arm_group_label>
    <arm_group_label>Intermediate-risk SMM</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone will be administered weekly</description>
    <arm_group_label>High-risk SMM and MM</arm_group_label>
    <arm_group_label>Intermediate-risk SMM</arm_group_label>
    <other_name>Dexasone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants that are diagnosed with MM, high- or intermediate-risk SMM in the iStopMM&#xD;
        study will be invited to participate in this study. Each patient must meet all the&#xD;
        following inclusion criteria to be enrolled in the study:&#xD;
&#xD;
          1. Age more than 18 years.&#xD;
&#xD;
          2. Active MM or&#xD;
&#xD;
          3. Smoldering myeloma, which is untreated, as defined by: Measurable M spike OR&#xD;
             pathological FLC ratio AND bone marrow PC% &gt; 10%&#xD;
&#xD;
          4. The following laboratory values obtained ≤ 30 days prior to registration&#xD;
&#xD;
               -  Calculated creatinine clearance ≥ 30mL/min (using CKD-EPI equation)&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt; 1000/mm3&#xD;
&#xD;
               -  Platelet count &gt; 75000/mm3&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  ALT and AST ≤ 3 x ULN&#xD;
&#xD;
          5. Measurable disease as defined by at least one of the following:&#xD;
&#xD;
               -  Serum monoclonal protein &gt; 1.0g/L&#xD;
&#xD;
               -  &gt; 200 mg of monoclonal protein in the urine on 24 hour electrophoresis&#xD;
&#xD;
               -  Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum&#xD;
                  immunoglobulin kappa to lambda free light chain ratio&#xD;
&#xD;
          6. Prior therapy for the treatment of solitary plasmacytoma is permitted, but &gt;7 days&#xD;
             should have elapsed from the last day of radiation. NOTE: Prior therapy with&#xD;
             clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted. Any&#xD;
             additional agents not listed must be approved by the Principal Investigator.&#xD;
&#xD;
          7. ECOG performance status 0, 1 or 2&#xD;
&#xD;
          8. Negative pregnancy test done ≤7 days prior to C1D1, for women of childbearing&#xD;
             potential only.&#xD;
&#xD;
          9. Willing to follow strict birth control measures as outlined in the protocol.&#xD;
&#xD;
         10. Female subjects: If they are of childbearing potential, agree to one of the following:&#xD;
&#xD;
             Practice 2 effective methods of contraception, at the same time, from the time of&#xD;
             signing the informed consent form through 90 days after the last dose of trial drug,&#xD;
             AND must also adhere to the guidelines of any treatment-specific pregnancy prevention&#xD;
             program (appendix 1), if applicable, OR Agree to practice true abstinence when this is&#xD;
             in line with the preferred and usual lifestyle of the subject. (Periodic abstinence&#xD;
             [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are&#xD;
             not acceptable methods of contraception.)&#xD;
&#xD;
         11. Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree&#xD;
             to one of the following: Agree to practice effective barrier contraception during the&#xD;
             entire trial treatment period and through 90 days after the last dose of trial drug,&#xD;
             OR Must also adhere to the guidelines of any treatment-specific pregnancy prevention&#xD;
             program (appendix 1), if applicable, OR Agree to practice true abstinence when this is&#xD;
             in line with the preferred and usual lifestyle of the subject. (Periodic abstinence&#xD;
             (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are&#xD;
             not acceptable methods of contraception). Willing to return to enrolling institution&#xD;
             for follow-up during the Active Treatment Phase of the trial. Agree not to donate&#xD;
             sperm for at least 90 days after the last dose of carfilzomib&#xD;
&#xD;
         12. Willing to provide samples for planned research&#xD;
&#xD;
         13. Life expectancy &gt; 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. MGUS or low-risk smoldering myeloma.&#xD;
&#xD;
          2. Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or&#xD;
             previously diagnosed with another malignancy and have any evidence of residual&#xD;
             disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type&#xD;
             are not excluded if they have undergone complete resection.&#xD;
&#xD;
          3. If any of the following exist at screening, subject will not be eligible for trial&#xD;
             because this trial involves an investigational agent whose genotoxic, mutagenic and&#xD;
             teratogenic effects on the developing fetus and newborn are unknown: Pregnant women&#xD;
             Nursing women Men or women of childbearing potential who are unwilling to employ&#xD;
             adequate contraception (per protocol)&#xD;
&#xD;
          4. Other co-morbidity which would interfere with subject's ability to participate in&#xD;
             trial, e.g. uncontrolled infection, uncompensated heart or lung disease&#xD;
&#xD;
          5. Other concurrent chemotherapy, or any ancillary therapy considered investigational.&#xD;
&#xD;
             NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and&#xD;
             are thus allowed while on protocol treatment.&#xD;
&#xD;
          6. Peripheral neuropathy &gt; Grade 3 on clinical examination or grade 2 with pain within 30&#xD;
             days prior to C1D1.&#xD;
&#xD;
          7. Major surgery ≤14 days prior to C1D1.&#xD;
&#xD;
          8. Evidence of current uncontrolled cardiovascular conditions, including hypertension,&#xD;
             cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial&#xD;
             infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality&#xD;
             at screening must be documented by the investigator as not medically relevant.&#xD;
&#xD;
          9. Known human immunodeficiency virus (HIV) positive.&#xD;
&#xD;
         10. Known hepatitis B surface antigen-positive status, or known or suspected active&#xD;
             hepatitis C infection.&#xD;
&#xD;
         11. Any medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with the completion of treatment according to this protocol.&#xD;
&#xD;
         12. Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal&#xD;
             antibodies or human proteins, or their excipients (refer to respective package inserts&#xD;
             or Investigator's Brochure), or known sensitivity to mammalian-derived products.&#xD;
&#xD;
             Known allergies, hypersensitivity, or intolerance to trial drugs.&#xD;
&#xD;
         13. Inability to comply with protocol/procedures.&#xD;
&#xD;
         14. LVEF &lt; 40% for patients treated with carfilzomib.&#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>Sigurdur Y Kristinsson, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Landspitali University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Landspitali University Hospital</name>
      <address>
        <city>Reykjavík</city>
        <zip>101</zip>
        <country>Iceland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iceland</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>August 14, 2019</last_update_submitted>
  <last_update_submitted_qc>August 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Smoldering Multiple Myeloma</keyword>
  <keyword>Carfilzomib</keyword>
  <keyword>Lenalidomide</keyword>
  <keyword>Screening</keyword>
  <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>Dexamethasone</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03815279
org study id: LSH-17-001
nct id: NCT03815279
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the efficacy of treating patients with intermediate
      risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and
      lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and
      carfilzomib.
This is an open label, single center, phase II study assessing the efficacy of treating
      patients with intermediate-risk smoldering myeloma (SMM) with combinational therapy with
      dexamethasone and lenalidomide and treating patients with high risk SMM and active multiple
      myeloma (MM) with combinational therapy with dexamethasone, lenalidomide and carfilzomib.
      Patients that are eligible for this study are participants in the IstopMM study
      (ClinicalTrials.gov number, NCT03327597) that are diagnosed with intermediate or high-risk
      SMM or active MM.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: An investigator initiated, academic, non-randomized, open-label phase 2 study that will assess carfilzomib, lenalidomide and dexamethasone regimen as treatment in patients with intermediate-risk (not carfilzomib) or high-risk SMM or active MM.
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of MRD negativity
time frame: 36 months after study enrollment
description: Minimal residual disease (MRD) as determined VDJ sequencing
measure: Progression free survival
time frame: Up until 3 years after treatment
description: Rates of progression free survival with progression being determined by IMWG response criteria
measure: Overall survival
time frame: Up until 3 years after treatment
description: Overall survival as determened by the Icelandic National Cause of Death Registry
arm group label: High-risk SMM and MM
arm group type: Experimental
description: Twelve cycles of Carfilzomib-Lenalidomide-Dexamethason. Each cycle is 28 days. Carfilzomib intravenous, days 1, 8 and 15 (starting dose, 20 mg/m2 on day 1 of cycle 1; target dose, 56 mg/m2 thereafter) during cycles 1 through 12.
Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks then 20 mg weekly for 16 weeks and thereafter 10 mg weekly for 16 weeks.
Maintenance (1 year):
Carfilzomib intravenous days 1 and 15 (56 mg/m2) during cycles 13 through 24. Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks Dexamethasone 10 mg weekly for 52 weeks.
arm group label: Intermediate-risk SMM
arm group type: Experimental
description: Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks, then 20 mg weekly for 16 weeks.
Maintenance (1 year):
Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks.
intervention type: Drug
intervention name: Carfilzomib
description: Carfilzomib will be administered intravenously three times per cycle (28 day cycles) for cycle 1-12. Thereafter twice per cycle for cycle 13-24
arm group label: High-risk SMM and MM
other name: Kyprolis
intervention type: Drug
intervention name: Lenalidomide
description: Lenalidomide PO once daily on days 1-21 of a 28 day cycle
arm group label: High-risk SMM and MM
arm group label: Intermediate-risk SMM
other name: Revlimid
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone will be administered weekly
arm group label: High-risk SMM and MM
arm group label: Intermediate-risk SMM
other name: Dexasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sigurdur Y Kristinsson, MD, PhD
role: Principal Investigator
affiliation: Landspitali University Hospital
facility: 
country: Iceland
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Smoldering Multiple Myeloma
mesh term: Dexamethasone
mesh term: Lenalidomide
sharing ipd: No