<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/NCT03012880</url>
  </required_header>
  <id_info>
    <org_study_id>MC1686</org_study_id>
    <secondary_id>NCI-2017-00007</secondary_id>
    <secondary_id>MC1686</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT03012880</nct_id>
  </id_info>
  <brief_title>Ixazomib Citrate, Lenalidomide, Dexamethasone, and Daratumumab in Treating Patients With Newly Diagnosed Multiple Myeloma</brief_title>
  <official_title>Phase 2 Trial of Ixazomib, Lenalidomide, Dexamethasone, and Daratumumab in Patients With Newly Diagnosed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</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>
      This phase II trial studies how well ixazomib citrate, lenalidomide, dexamethasone, and&#xD;
      daratumumab work in treating patients with newly diagnosed multiple myeloma. Ixazomib citrate&#xD;
      may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.&#xD;
      Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to&#xD;
      stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,&#xD;
      or by stopping them from spreading. Monoclonal antibodies, such as daratumumab, may block&#xD;
      cancer growth in different ways by targeting certain cells. Giving ixazomib citrate,&#xD;
      lenalidomide, dexamethasone, and daratumumab may work better in treating patients with newly&#xD;
      diagnosed multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the complete response rate (CR) of the four-drug combination of ixazomib,&#xD;
      lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic&#xD;
      multiple myeloma (MM).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the overall response rate (ORR), and very good partial response (VGPR) rate&#xD;
      with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab, when&#xD;
      used as initial therapy in patients with previously untreated symptomatic MM.&#xD;
&#xD;
      II. To determine the progression free survival and overall survival among patients with&#xD;
      previously untreated symptomatic MM following treatment with the four drug combination of&#xD;
      Ixazomib, lenalidomide, dexamethasone and daratumumab followed by ixazomib and daratumumab&#xD;
      maintenance till progression.&#xD;
&#xD;
      II. To determine the toxicities associated with the four drug combination of ixazomib,&#xD;
      lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic&#xD;
      MM.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To examine the proportion of minimal residual disease (MRD) negativity following induction&#xD;
      therapy with the four-drug combination of ixazomib, lenalidomide, dexamethasone and&#xD;
      daratumumab.&#xD;
&#xD;
      II. To assess the quality of life using patient completed Functional Assessment of Cancer&#xD;
      Treatment (FACT)/Gynecologic Oncology Group (GOG) questionnaires.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      INDUCTION PHASE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and&#xD;
      lenalidomide PO on days 1-21. Patients receive daratumumab intravenously (IV) over 3-7 hours&#xD;
      on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on&#xD;
      day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and&#xD;
      22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab&#xD;
      IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from&#xD;
      registration in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 or 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 12, 2017</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">May 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients who achieve a confirmed Complete Response (CR)</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be estimated by the number of patients who achieve a stringent complete response (sCR), CR, VGPR or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>The time from registration to death due to any cause, assessed up to 2 years</time_frame>
    <description>The distribution of overall survival will be estimated using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>The time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years</time_frame>
    <description>The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of &gt;= Very Good Partial Response (VGPR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be estimated by the number of patients with a VGPR, CR, or Stringent Complete Response (sCR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Minor Response Development (MRD)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be assessed on bone marrow aspirate in all patients achieving CR. The proportion of patients who achieve MRD negative status will be estimated by the number of patients who are MRD negative divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Neurotoxicity</measure>
    <time_frame>Baseline up to 2 years</time_frame>
    <description>The FACT/GOG neurotoxicity questionnaire will be completed. Patients will be evaluated by overall score for each questionnaire at each time point and changes over time will be calculated. These measures will be correlated with outcome using Fisher's exact test and Kaplan-Meier methods where appropriate.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
    <other_name>Anti-CD38 Monoclonal Antibody</other_name>
    <other_name>Darzalex</other_name>
    <other_name>HuMax-CD38</other_name>
    <other_name>JNJ-54767414</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
    <other_name>Aacidexam</other_name>
    <other_name>Adexone</other_name>
    <other_name>Aknichthol Dexa</other_name>
    <other_name>Alba-Dex</other_name>
    <other_name>Alin</other_name>
    <other_name>Alin Depot</other_name>
    <other_name>Alin Oftalmico</other_name>
    <other_name>Amplidermis</other_name>
    <other_name>Anemul mono</other_name>
    <other_name>Auricularum</other_name>
    <other_name>Auxiloson</other_name>
    <other_name>Baycuten</other_name>
    <other_name>Baycuten N</other_name>
    <other_name>Cortidexason</other_name>
    <other_name>Cortisumman</other_name>
    <other_name>Decacort</other_name>
    <other_name>Decadrol</other_name>
    <other_name>Decadron</other_name>
    <other_name>Decalix</other_name>
    <other_name>Decameth</other_name>
    <other_name>Decasone R.p.</other_name>
    <other_name>Dectancyl</other_name>
    <other_name>Dekacort</other_name>
    <other_name>Deltafluorene</other_name>
    <other_name>Deronil</other_name>
    <other_name>Desamethasone</other_name>
    <other_name>Desameton</other_name>
    <other_name>Dexa-Mamallet</other_name>
    <other_name>Dexa-Rhinosan</other_name>
    <other_name>Dexa-Scheroson</other_name>
    <other_name>Dexa-sine</other_name>
    <other_name>Dexacortal</other_name>
    <other_name>Dexacortin</other_name>
    <other_name>Dexafarma</other_name>
    <other_name>Dexafluorene</other_name>
    <other_name>Dexalocal</other_name>
    <other_name>Dexamecortin</other_name>
    <other_name>Dexameth</other_name>
    <other_name>Dexamethasonum</other_name>
    <other_name>Dexamonozon</other_name>
    <other_name>Dexapos</other_name>
    <other_name>Dexinoral</other_name>
    <other_name>Dexone</other_name>
    <other_name>Dinormon</other_name>
    <other_name>Fluorodelta</other_name>
    <other_name>Fortecortin</other_name>
    <other_name>Gammacorten</other_name>
    <other_name>Hexadecadrol</other_name>
    <other_name>Hexadrol</other_name>
    <other_name>Lokalison-F</other_name>
    <other_name>Loverine</other_name>
    <other_name>Methylfluorprednisolone</other_name>
    <other_name>Millicorten</other_name>
    <other_name>Mymethasone</other_name>
    <other_name>Orgadrone</other_name>
    <other_name>Spersadex</other_name>
    <other_name>Visumetazone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixazomib Citrate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
    <other_name>MLN-9708</other_name>
    <other_name>MLN9708</other_name>
    <other_name>Ninlaro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>CC5013</other_name>
    <other_name>CDC 501</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Calculated creatinine clearance (using Cockcroft-Gault equation) &gt;= 30 mL/min&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3&#xD;
&#xD;
          -  Untransfused platelet count &gt;= 75000/mm^3&#xD;
&#xD;
          -  Hemoglobin &gt;= 8.0 g/dL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 2.5 x ULN&#xD;
&#xD;
          -  Measurable disease of multiple myeloma as defined by at least ONE of the following:&#xD;
&#xD;
               -  Serum monoclonal protein &gt;= 1.0 g/dL&#xD;
&#xD;
               -  &gt;= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis&#xD;
&#xD;
               -  Serum immunoglobulin free light chain &gt;= 10 mg/dL AND abnormal serum&#xD;
                  immunoglobulin kappa to lambda free light chain ratio&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2&#xD;
&#xD;
          -  Previously untreated for myeloma or have received no more than one cycle of any&#xD;
             treatment regimen; NOTE: Prior radiation therapy for the treatment of solitary&#xD;
             plasmacytoma is permitted; prior therapy with clarithromycin, dehydroepiandrosterone&#xD;
             (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents&#xD;
             not listed must be approved by the principal investigator&#xD;
&#xD;
          -  Provide informed written consent&#xD;
&#xD;
          -  Negative pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Willing to follow strict birth control measures&#xD;
&#xD;
               -  Female patients: if they are of childbearing potential, agree to one of the&#xD;
                  following:&#xD;
&#xD;
                    -  Practice 2 effective methods of contraception, at the same time, from the&#xD;
                       time of signing the informed consent form through 90 days after the last&#xD;
                       dose of study drug, AND must also adhere to the guidelines of any treatment&#xD;
                       specific pregnancy prevention program, if applicable, OR&#xD;
&#xD;
                    -  Agree to practice true abstinence when this is in line with the preferred&#xD;
                       and usual lifestyle of the subject; (periodic abstinence [e.g., calendar,&#xD;
                       ovulation, symptothermal, post-ovulation methods] and withdrawal are not&#xD;
                       acceptable methods of contraception)&#xD;
&#xD;
               -  Male patients: even if surgically sterilized (i.e., status post-vasectomy), must&#xD;
                  agree to one of the following:&#xD;
&#xD;
                    -  Agree to practice effective barrier contraception during the entire study&#xD;
                       treatment period and through 90 days after the last dose of study drug, OR&#xD;
&#xD;
                    -  Must also adhere to the guidelines of any treatment-specific pregnancy&#xD;
                       prevention program, if applicable, OR&#xD;
&#xD;
                    -  Agree to practice true abstinence when this is in line with the preferred&#xD;
                       and usual lifestyle of the subject; (periodic abstinence (eg, calendar,&#xD;
                       ovulation, symptothermal, post-ovulation methods] and withdrawal are not&#xD;
                       acceptable methods of contraception)&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up (during the active monitoring&#xD;
             phase of the study)&#xD;
&#xD;
          -  Willing to follow the requirements of the Revlimid Risk Evaluation and Mitigation&#xD;
             Strategy (REMS) program&#xD;
&#xD;
          -  Willing to provide bone marrow and blood samples for planned research&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma&#xD;
&#xD;
          -  Diagnosed or treated for another malignancy =&lt; 2 years prior to registration or&#xD;
             previously diagnosed with another malignancy and have any evidence of residual&#xD;
             disease; NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type&#xD;
             are not excluded if they have undergone complete resection&#xD;
&#xD;
          -  Any of the following:&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Men or women of childbearing potential who are unwilling to employ adequate&#xD;
                  contraception&#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 &gt;= grade 2 on clinical examination or grade 1 with pain during&#xD;
             the screening period&#xD;
&#xD;
          -  Major surgery =&lt; 14 days prior to registration&#xD;
&#xD;
          -  Systemic treatment with strong CYP3A4 inducers (rifampin, rifapentine, rifabutin,&#xD;
             carbamazepine, phenytoin, phenobarbital, St. John's wort) =&lt; 14 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Evidence of current uncontrolled cardiovascular conditions, including hypertension,&#xD;
             cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial&#xD;
             infarction =&lt; 6 months; Note: Prior to entry, any ECG abnormality at screening must be&#xD;
             documented by the investigator as not medically relevant&#xD;
&#xD;
          -  Radiotherapy =&lt; 14 days prior to registration; NOTE: If the involved field is small, 7&#xD;
             days will be considered a sufficient interval between treatment and administration of&#xD;
             the ixazomib&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) positive&#xD;
&#xD;
          -  Known hepatitis B surface antigen-positive status, or known or suspected active&#xD;
             hepatitis C infection&#xD;
&#xD;
          -  Any serious 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;
          -  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 gastrointestinal (GI) disease or GI procedure that could interfere with the oral&#xD;
             absorption or tolerance of ixazomib, lenalidomide or dexamethasone including&#xD;
             difficulty swallowing&#xD;
&#xD;
          -  Diarrhea &gt; grade 1, based on the National Cancer Institute (NCI) Common Terminology&#xD;
             Criteria for Adverse Events (CTCAE) grading, in the absence of antidiarrheals&#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</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>June 16, 2023</last_update_submitted>
  <last_update_submitted_qc>June 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Daratumumab</mesh_term>
    <mesh_term>Ixazomib</mesh_term>
    <mesh_term>Ichthammol</mesh_term>
    <mesh_term>BB 1101</mesh_term>
    <mesh_term>Glycine</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/NCT03012880
org study id: MC1686
secondary id: NCI-2017-00007
secondary id: MC1686
secondary id: P30CA015083
nct id: NCT03012880
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well ixazomib citrate, lenalidomide, dexamethasone, and
      daratumumab work in treating patients with newly diagnosed multiple myeloma. Ixazomib citrate
      may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
      Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to
      stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
      or by stopping them from spreading. Monoclonal antibodies, such as daratumumab, may block
      cancer growth in different ways by targeting certain cells. Giving ixazomib citrate,
      lenalidomide, dexamethasone, and daratumumab may work better in treating patients with newly
      diagnosed multiple myeloma.
PRIMARY OBJECTIVES:

      I. To determine the complete response rate (CR) of the four-drug combination of ixazomib,
      lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic
      multiple myeloma (MM).

      SECONDARY OBJECTIVES:

      I. To determine the overall response rate (ORR), and very good partial response (VGPR) rate
      with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab, when
      used as initial therapy in patients with previously untreated symptomatic MM.

      II. To determine the progression free survival and overall survival among patients with
      previously untreated symptomatic MM following treatment with the four drug combination of
      Ixazomib, lenalidomide, dexamethasone and daratumumab followed by ixazomib and daratumumab
      maintenance till progression.

      II. To determine the toxicities associated with the four drug combination of ixazomib,
      lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic
      MM.

      TERTIARY OBJECTIVES:

      I. To examine the proportion of minimal residual disease (MRD) negativity following induction
      therapy with the four-drug combination of ixazomib, lenalidomide, dexamethasone and
      daratumumab.

      II. To assess the quality of life using patient completed Functional Assessment of Cancer
      Treatment (FACT)/Gynecologic Oncology Group (GOG) questionnaires.

      OUTLINE:

      INDUCTION PHASE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and
      lenalidomide PO on days 1-21. Patients receive daratumumab intravenously (IV) over 3-7 hours
      on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on
      day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and
      22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or
      unacceptable toxicity.

      MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab
      IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from
      registration in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 or 6 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients who achieve a confirmed Complete Response (CR)
time frame: Up to 2 years
measure: Incidence of adverse events
time frame: Up to 2 years
description: The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
measure: Overall Response Rate (ORR)
time frame: Up to 2 years
description: Will be estimated by the number of patients who achieve a stringent complete response (sCR), CR, VGPR or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
measure: Overall Survival (OS)
time frame: The time from registration to death due to any cause, assessed up to 2 years
description: The distribution of overall survival will be estimated using the method of Kaplan-Meier.
measure: Progression free survival
time frame: The time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years
description: The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
measure: Rate of >= Very Good Partial Response (VGPR)
time frame: Up to 2 years
description: Will be estimated by the number of patients with a VGPR, CR, or Stringent Complete Response (sCR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
measure: Minor Response Development (MRD)
time frame: Up to 2 years
description: Will be assessed on bone marrow aspirate in all patients achieving CR. The proportion of patients who achieve MRD negative status will be estimated by the number of patients who are MRD negative divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.
measure: Neurotoxicity
time frame: Baseline up to 2 years
description: The FACT/GOG neurotoxicity questionnaire will be completed. Patients will be evaluated by overall score for each questionnaire at each time point and changes over time will be calculated. These measures will be correlated with outcome using Fisher's exact test and Kaplan-Meier methods where appropriate.
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
arm group type: Experimental
description: INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Daratumumab
description: Given IV
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
other name: Anti-CD38 Monoclonal Antibody
other name: Darzalex
other name: HuMax-CD38
other name: JNJ-54767414
intervention type: Drug
intervention name: Dexamethasone
description: Given PO
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
other name: Aacidexam
other name: Adexone
other name: Aknichthol Dexa
other name: Alba-Dex
other name: Alin
other name: Alin Depot
other name: Alin Oftalmico
other name: Amplidermis
other name: Anemul mono
other name: Auricularum
other name: Auxiloson
other name: Baycuten
other name: Baycuten N
other name: Cortidexason
other name: Cortisumman
other name: Decacort
other name: Decadrol
other name: Decadron
other name: Decalix
other name: Decameth
other name: Decasone R.p.
other name: Dectancyl
other name: Dekacort
other name: Deltafluorene
other name: Deronil
other name: Desamethasone
other name: Desameton
other name: Dexa-Mamallet
other name: Dexa-Rhinosan
other name: Dexa-Scheroson
other name: Dexa-sine
other name: Dexacortal
other name: Dexacortin
other name: Dexafarma
other name: Dexafluorene
other name: Dexalocal
other name: Dexamecortin
other name: Dexameth
other name: Dexamethasonum
other name: Dexamonozon
other name: Dexapos
other name: Dexinoral
other name: Dexone
other name: Dinormon
other name: Fluorodelta
other name: Fortecortin
other name: Gammacorten
other name: Hexadecadrol
other name: Hexadrol
other name: Lokalison-F
other name: Loverine
other name: Methylfluorprednisolone
other name: Millicorten
other name: Mymethasone
other name: Orgadrone
other name: Spersadex
other name: Visumetazone
intervention type: Drug
intervention name: Ixazomib Citrate
description: Given PO
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
other name: MLN-9708
other name: MLN9708
other name: Ninlaro
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shaji Kumar
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Lenalidomide
mesh term: Daratumumab
mesh term: Ixazomib
mesh term: Ichthammol
mesh term: BB 1101
mesh term: Glycine