<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/NCT03289299</url>
  </required_header>
  <id_info>
    <org_study_id>BS001</org_study_id>
    <secondary_id>20159417</secondary_id>
    <secondary_id>54767414MMY2009</secondary_id>
    <secondary_id>RV-CL-MM-IMF-008479</secondary_id>
    <nct_id>NCT03289299</nct_id>
  </id_info>
  <brief_title>Aggressive Smoldering Curative Approach Evaluating Novel Therapies and Transplant</brief_title>
  <acronym>ASCENT</acronym>
  <official_title>Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation, and Maintenance in Subjects With High Risk Smoldering Multiple Myeloma (SMM)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Myeloma Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Janssen Scientific Affairs, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Trevie, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>International Myeloma Foundation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in&#xD;
      subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in&#xD;
      3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each&#xD;
      cycle is 28 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and&#xD;
      dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains&#xD;
      incurable with the current approaches. The typical natural history of myeloma is one of&#xD;
      repeated relapses, accompanied by genetic evolution and development of new abnormalities,&#xD;
      which are often responsible for drug resistance. The presence of a precursor phase of&#xD;
      smoldering myeloma, and the ability to identify those at the highest risk of progression,&#xD;
      sets the stage to examine the possibility that we can cure the disease through early&#xD;
      intervention. In order to potentially achieve this, we need to develop a highly effective&#xD;
      combination that includes the most active drugs from different classes. Carfilzomib in&#xD;
      combination with lenalidomide and dexamethasone results in high response rates and deep&#xD;
      responses in subjects with newly diagnosed myeloma. Daratumumab in combination with&#xD;
      lenalidomide results in high response rates in relapsed refractory disease. All these drugs&#xD;
      are well tolerated and subjects are able to stay on them long term as a maintenance&#xD;
      treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone&#xD;
      presents the potential to enhance the effectiveness of the regimens. We hypothesize that this&#xD;
      combination will lead to deep response including a higher proportion of minimal residual&#xD;
      disease (MRD) negative disease among those with high risk smoldering myeloma and may&#xD;
      translate into cure or long term disease quiescence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 25, 2018</start_date>
  <completion_date type="Anticipated">November 15, 2031</completion_date>
  <primary_completion_date type="Anticipated">November 15, 2023</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>Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stringent complete response rate</measure>
    <time_frame>During treatment</time_frame>
    <description>A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MRD negativity after each treatment phase</measure>
    <time_frame>6 months, 12 months, and 2 years</time_frame>
    <description>MRD negativity after induction, consolidation, and maintenance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRD negativity at 1 year post treatment</measure>
    <time_frame>1 year post treatment</time_frame>
    <description>Persistent MRD negativity rate will be evaluated at 1 year after completion of planned treatment consisting of induction, consolidation, and maintenance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>up to 10 years post registration</time_frame>
    <description>time of registration to death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>up to 10 years post registration</time_frame>
    <description>the time from registration to the earliest date of documentation of disease progression or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>all eligible subjects that have initiated treatment will be considered evaluable for assessing adverse even rates. The maximum grade for each type of adverse event will be recorded. Relationship to trial treatment will be taken into consideration.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Smoldering Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-high dose treatment in 3 phases Induction 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Consolidation 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Maintenance 12 cycles: lenalidomide, daratumumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>25 mg po given on days 1-21 of each cycle during the induction and consolidation phases.&#xD;
10 mg po given on days 1-21 of each cycle during the maintenance phase.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24.</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years and ≤ 80 years&#xD;
&#xD;
          -  High risk smoldering myeloma, which is untreated, as defined by either of the two&#xD;
             following criteria:&#xD;
&#xD;
               1. Presence of any two of the following: Serum M spike &gt; 2 gm/dL OR an involved to&#xD;
                  uninvolved free light chain (FLC) ratio &gt; 20 OR bone marrow PC% &gt; 20%&#xD;
&#xD;
               2. Total score of 9 or above using the following scoring system:&#xD;
&#xD;
        FLC Ratio &gt;10-25 = 2 &gt;25-40 = 3 &gt; 40 = 5&#xD;
&#xD;
        Serum M Protein (g/dL) &gt;1.5-3 = 3 &gt;3 = 4&#xD;
&#xD;
        BMPC% &gt;15-20 = 2 &gt;20-30 = 3 &gt;30-40 = 5 &gt;40 = 6&#xD;
&#xD;
        FISH abnormality (t(4,14), t(14,16), 1q gain, or del13q = 2&#xD;
&#xD;
          -  The following laboratory values obtained 14 days prior to registration.&#xD;
&#xD;
          -  Calculated creatinine clearance (using Cockcroft-Gault equation below)* ≥ 30 mL/min&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1000/mm3 (without the use of growth factors)&#xD;
&#xD;
          -  Platelet count ≥ 75000/mm3&#xD;
&#xD;
          -  Hemoglobin ≥8.0 g/dL&#xD;
&#xD;
          -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN&#xD;
&#xD;
          -  left ventricular ejection fraction (LVEF) ≥ 40%&#xD;
&#xD;
          -  LVEF ≥ 40%&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Appendix&#xD;
             VII)&#xD;
&#xD;
          -  Previously untreated.&#xD;
&#xD;
          -  Provide informed written consent.&#xD;
&#xD;
          -  Negative pregnancy test done ≤14 days prior to cycle 1 day 1, for women of&#xD;
             childbearing potential only.&#xD;
&#xD;
          -  All study participants must be registered into the mandatory Revlimid Risk Evaluation&#xD;
             and Mitigation Strategy (REMS®) program and be willing and able to comply with the&#xD;
             requirements of the REMS® program.&#xD;
&#xD;
          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as&#xD;
             required in the Revlimid REMS® program.&#xD;
&#xD;
          -  Willing to follow strict birth control measures as outlined in the protocol.&#xD;
&#xD;
        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, if applicable, OR&#xD;
&#xD;
          -  Agree to practice true abstinence when this is in line with the preferred and usual&#xD;
             lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation,&#xD;
             symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of&#xD;
             contraception.)&#xD;
&#xD;
        Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree to&#xD;
        one of the following:&#xD;
&#xD;
          -  Agree to practice effective barrier contraception during the entire trial treatment&#xD;
             period and through 90 days after the last dose of trial drug, OR&#xD;
&#xD;
          -  Must also adhere to the guidelines of any treatment-specific pregnancy prevention&#xD;
             program, if applicable, OR&#xD;
&#xD;
          -  Agree to practice true abstinence when this is in line with the preferred and usual&#xD;
             lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation,&#xD;
             symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of&#xD;
             contraception).&#xD;
&#xD;
               -  Willing to return to enrolling institution for follow-up during the Active&#xD;
                  Treatment Phase of the trial.&#xD;
&#xD;
               -  Male subjects must agree not to donate sperm for at least 90 days after the last&#xD;
                  dose of study treatment.&#xD;
&#xD;
               -  Willing to provide samples for planned research&#xD;
&#xD;
               -  Life expectancy &gt; 6 months&#xD;
&#xD;
               -  Able to take aspirin (325 mg) daily as prophylactic anticoagulation. Subjects&#xD;
                  intolerant to aspirin may use warfarin or low dose molecular weight heparin,&#xD;
                  novel oral anticoagulants, or low dose molecular weight heparin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering&#xD;
             myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ&#xD;
             involvement or patients with extramedullary disease.&#xD;
&#xD;
          -  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;
          -  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:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception (per protocol)&#xD;
&#xD;
          -  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;
          -  Other concurrent chemotherapy, or any ancillary therapy considered investigational.&#xD;
             NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and&#xD;
             are thus allowed while on protocol treatment.&#xD;
&#xD;
          -  Peripheral neuropathy ≥ Grade 3 on clinical examination or grade 2 with pain within 30&#xD;
             days prior to C1D1.&#xD;
&#xD;
          -  Major surgery ≤14 days prior to C1D1.&#xD;
&#xD;
          -  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;
          -  New York Heart Association (NYHA) II, III, IV heart failure&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) positive.&#xD;
&#xD;
          -  Seropositive for hepatitis B (defined by a positive test for hepatitis B surface&#xD;
             antigen [HBsAg]). Subjects with resolved infection (ie., subjects who are HBsAg&#xD;
             negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or&#xD;
             antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time&#xD;
             polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.&#xD;
             Those who are PCR positive will be excluded. EXCEPTION: subjects with serologic&#xD;
             findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic&#xD;
             marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV&#xD;
             DNA by PCR.&#xD;
&#xD;
          -  Known or suspected active hepatitis C infection.&#xD;
&#xD;
          -  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;
          -  Prior radiation therapy for bony lesions or plasmacytomas&#xD;
&#xD;
          -  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. Known&#xD;
             allergies, hypersensitivity, or intolerance to trial drugs.&#xD;
&#xD;
          -  Inability to comply with protocol/procedures.&#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>Shaji Kumar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Brian Durie, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>International Myeloma Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</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>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Cancer Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>July 8, 2022</last_update_submitted>
  <last_update_submitted_qc>July 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>myeloma</keyword>
  <keyword>MRD</keyword>
  <keyword>smoldering</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>
    <mesh_term>Daratumumab</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/NCT03289299
org study id: BS001
secondary id: 20159417
secondary id: 54767414MMY2009
secondary id: RV-CL-MM-IMF-008479
nct id: NCT03289299
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in
      subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in
      3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each
      cycle is 28 days.
This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and
      dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains
      incurable with the current approaches. The typical natural history of myeloma is one of
      repeated relapses, accompanied by genetic evolution and development of new abnormalities,
      which are often responsible for drug resistance. The presence of a precursor phase of
      smoldering myeloma, and the ability to identify those at the highest risk of progression,
      sets the stage to examine the possibility that we can cure the disease through early
      intervention. In order to potentially achieve this, we need to develop a highly effective
      combination that includes the most active drugs from different classes. Carfilzomib in
      combination with lenalidomide and dexamethasone results in high response rates and deep
      responses in subjects with newly diagnosed myeloma. Daratumumab in combination with
      lenalidomide results in high response rates in relapsed refractory disease. All these drugs
      are well tolerated and subjects are able to stay on them long term as a maintenance
      treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone
      presents the potential to enhance the effectiveness of the regimens. We hypothesize that this
      combination will lead to deep response including a higher proportion of minimal residual
      disease (MRD) negative disease among those with high risk smoldering myeloma and may
      translate into cure or long term disease quiescence.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles).
primary purpose: Treatment
masking: None (Open Label)
measure: Stringent complete response rate
time frame: During treatment
description: A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.
measure: MRD negativity after each treatment phase
time frame: 6 months, 12 months, and 2 years
description: MRD negativity after induction, consolidation, and maintenance
measure: MRD negativity at 1 year post treatment
time frame: 1 year post treatment
description: Persistent MRD negativity rate will be evaluated at 1 year after completion of planned treatment consisting of induction, consolidation, and maintenance.
measure: Overall Survival
time frame: up to 10 years post registration
description: time of registration to death due to any cause
measure: Progression-free survival
time frame: up to 10 years post registration
description: the time from registration to the earliest date of documentation of disease progression or death due to any cause
measure: Adverse events
time frame: 2 years
description: all eligible subjects that have initiated treatment will be considered evaluable for assessing adverse even rates. The maximum grade for each type of adverse event will be recorded. Relationship to trial treatment will be taken into consideration.
arm group label: Arm A
arm group type: Experimental
description: Non-high dose treatment in 3 phases Induction 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Consolidation 6 cycles: carfilzomib, lenalidomide, daratumumab, dexamethasone Maintenance 12 cycles: lenalidomide, daratumumab
intervention type: Drug
intervention name: Carfilzomib
description: 56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study.
arm group label: Arm A
intervention type: Drug
intervention name: Lenalidomide
description: 25 mg po given on days 1-21 of each cycle during the induction and consolidation phases.
10 mg po given on days 1-21 of each cycle during the maintenance phase.
arm group label: Arm A
intervention type: Drug
intervention name: Daratumumab
description: 16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24.
arm group label: Arm A
intervention type: Drug
intervention name: Dexamethasone
description: 40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12
arm group label: Arm A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shaji Kumar, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Brian Durie, MD
role: Principal Investigator
affiliation: International Myeloma Foundation
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country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Smoldering Multiple Myeloma
mesh term: Dexamethasone
mesh term: Lenalidomide
mesh term: Daratumumab
sharing ipd: Undecided