<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/NCT03763162</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0512</org_study_id>
    <secondary_id>NCI-2018-02830</secondary_id>
    <secondary_id>2018-0512</secondary_id>
    <nct_id>NCT03763162</nct_id>
  </id_info>
  <brief_title>Daratumumab, Bortezomib, and Dexamethasone Followed by Daratumumab, Ixazomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>A Phase 2 Study of Daratumumab, Bortezomib, and Dexamethasone (DVd), Followed by Daratumumab, Ixazomib, and Dexamethasone (DId) for Relapsed and/or Refractory Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well daratumumab, bortezomib, and dexamethasone followed by&#xD;
      daratumumab, ixazomib, and dexamethasone in treating patients with multiple myeloma that has&#xD;
      come back (relapsed) or does not response to treatment (refractory). Immunotherapy with&#xD;
      monoclonal antibodies, such as daratumumab, may help the body's immune system attack the&#xD;
      cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in&#xD;
      chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Bortezomib and ixazomib may stop the growth of cancer cells by blocking some of&#xD;
      the enzymes needed for cell growth. Giving daratumumab, bortezomib, and dexamethasone&#xD;
      followed by daratumumab, ixazomib, and dexamethasone may work better and help to control&#xD;
      cancer in patients with multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the progression-free survival of subjects with daratumumab, bortezomib, and&#xD;
      dexamethasone (DVd) treatment followed by daratumumab, ixazomib, and dexamethasone (DId)&#xD;
      treatment.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate overall response rate (ORR) as assessed by International Myeloma Working Group&#xD;
      Criteria (IMWG).&#xD;
&#xD;
      II. To evaluate time to response (TTR). III. To evaluate time to progression (TTP). IV. To&#xD;
      evaluate duration of response (DOR). V. To evaluate overall survival (OS). VI. To evaluate&#xD;
      the safety and tolerability. VII. To evaluate minimal residual disease (MRD) rate. VIII. To&#xD;
      evaluate quality of life (QoL) using the Treatment Satisfaction Questionnaire for Medication&#xD;
      (TSMQ-9) and European Organization for the Research and Treatment of Cancer Quality of Life&#xD;
      Questionnaire (EORTC QLQ-C30) patient reported questionnaires.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate biomarkers of response to treatment and mechanisms of resistance with&#xD;
      pretreatment and post-treatment bone marrow and blood samples with deoxyribonucleic acid&#xD;
      (DNA) and ribonucleic acid (RNA) sequencing and immune profiling by flow cytometry.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive daratumumab intravenously (IV) over 3.5-6.5 hours on days 1, 8, and 15,&#xD;
      bortezomib subcutaneously (SC) on days 1, 4, 8, and 11, and dexamethasone IV over 15 minutes&#xD;
      on days 1, 8, and 15 and orally (PO) on days 2, 4, 5, 9, 11, 12, and 16. Treatment repeats&#xD;
      every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
      Patients then receive daratumumab IV over 3.5 hours on days 1 and 15 of cycles 4-7 and day 1&#xD;
      of subsequent cycles, ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes&#xD;
      or PO once weekly. Cycles repeat every 28 days in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study, patients are followed up at 30 days and then periodically for up&#xD;
      to 24 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 17, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>Progression free survival (PFS)</measure>
    <time_frame>From the date of first dose of any study drug treatment to the date of first documentation of progressive disease, or death due to any cause, whichever occurs first, assessed up to 18 months</time_frame>
    <description>Will be assessed by International Myeloma Working Group Criteria (IMWG).</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Recurrent Plasma Cell Myeloma</condition>
  <condition>Refractory Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive daratumumab IV over 3.5-6.5 hours on days 1, 8, and 15, bortezomib SC on days 1, 4, 8, and 11, and dexamethasone IV over 15 minutes on days 1, 8, and 15 and PO on days 2, 4, 5, 9, 11, 12, and 16. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive daratumumab IV over 3.5 hours on days 1 and 15 of cycles 4-7 and day 1 of subsequent cycles, ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO once weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)</arm_group_label>
    <other_name>[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid</other_name>
    <other_name>LDP 341</other_name>
    <other_name>MLN341</other_name>
    <other_name>PS-341</other_name>
    <other_name>PS341</other_name>
    <other_name>Velcade</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)</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 IV or PO</description>
    <arm_group_label>Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)</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>Baycadron</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>Decadron DP</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>Dexamethasone Intensol</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>Dxevo</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>TaperDex</other_name>
    <other_name>Visumetazone</other_name>
    <other_name>ZoDex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixazomib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)</arm_group_label>
    <other_name>MLN-2238</other_name>
    <other_name>MLN2238</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have histologically confirmed diagnosis of multiple myeloma&#xD;
&#xD;
          -  Subjects must have measurable disease, as defined by at least one of the following:&#xD;
&#xD;
               -  Serum monoclonal protein M-protein level &gt;= 0.5 g/dL&#xD;
&#xD;
               -  Urinary M-protein excretion of &gt;= 200 mg over a 24-hour period&#xD;
&#xD;
               -  Involved free light chain level &gt;= 10 mg/dL, along with an abnormal free light&#xD;
                  chain ratio&#xD;
&#xD;
          -  Subjects must have disease that has relapsed and/or refractory after their most recent&#xD;
             therapy, with progressive disease (PD) being defined as an increase of 25% from the&#xD;
             lowest response value in any one or more of the following:&#xD;
&#xD;
               -  Serum M-component protein (the absolute increase must be &gt;= 0.5 g/dL) and/or&#xD;
&#xD;
               -  Urine M-component protein (the absolute increase must be &gt;= 200 mg/24 hours)&#xD;
                  and/or&#xD;
&#xD;
               -  Only in subjects without a measurable serum and urine M protein level: the&#xD;
                  difference between involved and uninvolved free light chain (FLC) levels&#xD;
                  (absolute increase) must be &gt; 10 mg/dL&#xD;
&#xD;
               -  Definite development of new bone lesions or soft tissue plasmacytomas or definite&#xD;
                  increase in the size of existing bone lesions or soft tissue plasmacytomas&#xD;
&#xD;
               -  Development of hypercalcemia (corrected serum calcium &gt; 11.5 mg/dL) that can be&#xD;
                  attributed solely to the plasma cell proliferative disorder&#xD;
&#xD;
          -  Subjects with one to three lines of therapy for their disease with a prior therapy is&#xD;
             defined as 2 or more cycles of therapy given as a treatment plan for multiple myeloma&#xD;
             (MM) (e.g. a single-agent or combination therapy or a sequence of planned treatments&#xD;
             such as induction therapy followed by autologous stem cell transplant (SCT) and then&#xD;
             consolidation and/or maintenance therapy)&#xD;
&#xD;
          -  Subjects must have achieved a partial response or better to at least one prior line of&#xD;
             therapy&#xD;
&#xD;
          -  Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status&#xD;
             and/or other performance status 0, 1, or 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,000/mm^3 without growth factors within 2 weeks of&#xD;
             initiation of treatment&#xD;
&#xD;
          -  Platelets &gt;= 75,000/mm^3&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal (ULN). In subjects with&#xD;
             documents Gilbert's syndrome, total bilirubin =&lt; 2 x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase&#xD;
             (SGOT)/alkaline phosphatase (ALT) serum glutamic pyruvic transaminase (SGPT) =&lt; 3 x&#xD;
             ULN&#xD;
&#xD;
          -  Creatinine clearance &gt;= 30 mL/min/1.73 m^2&#xD;
&#xD;
          -  Subjects must be willing to give written consent before performance of any study&#xD;
             related procedures not part of standard medical care, with the understanding that&#xD;
             consent may be withdrawn by the subject at any time without prejudice to future&#xD;
             medical care&#xD;
&#xD;
          -  Female subjects who:&#xD;
&#xD;
               -  Are postmenopausal for at least 1 year before the screening visit, OR&#xD;
&#xD;
               -  Are surgically sterile, OR&#xD;
&#xD;
               -  If they are of childbearing potential, agree to practice 2 effective methods of&#xD;
                  contraception, at the same time, from the time of signing the informed consent&#xD;
                  form through 90 days after the last dose of study drug, OR&#xD;
&#xD;
               -  Agree to practice true abstinence when this is in line with the preferred and&#xD;
                  usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation,&#xD;
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods&#xD;
                  of contraception)&#xD;
&#xD;
          -  Male subjects, even if surgically sterilized (i.e., status post-vasectomy), must agree&#xD;
             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;
               -  Agree to practice true abstinence when this is in line with the preferred and&#xD;
                  usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation,&#xD;
                  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods&#xD;
                  of contraception)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who received prior ixazomib at any time or daratumumab or other anti-CD38&#xD;
             therapies, except as part of initial therapy if this was stopped to move on to SCT and&#xD;
             the subject did not progress on anti-CD38 treatment&#xD;
&#xD;
          -  Subjects are refractory to bortezomib or carfilzomib at the last exposure before this&#xD;
             study (defined as subject having PD while receiving bortezomib or carfilzomib therapy&#xD;
             or within 60 days after ending bortezomib or carfilzomib therapy)&#xD;
&#xD;
          -  Subjects with known allergy to any of the study medications or their analogues&#xD;
&#xD;
          -  Subjects planning to undergo SCT prior to PD on this study (i.e., these subjects&#xD;
             should not be enrolled in order to reduce disease burden prior to transplant)&#xD;
&#xD;
          -  Subjects receiving systemic treatment with strong cytochrome P450, family 3, subfamily&#xD;
             A (CYP3A) inducers (e.g. rifampin, rifapentine, rifabutin, carbamazepine, phenytoin,&#xD;
             phenobarbital) or use of St. John's wort within 14 days before randomization&#xD;
&#xD;
          -  Subjects must have completed their most recent drug therapy directed at multiple&#xD;
             myeloma in the following timeframes:&#xD;
&#xD;
               -  Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy,&#xD;
                  retinoid therapy, hormonal therapy, or investigational agent) within 30 days of&#xD;
                  study day 1&#xD;
&#xD;
               -  Corticosteroids at least 3 weeks prior to starting therapy, except for a dose&#xD;
                  equivalent to dexamethasone of =&lt; 4 mg/day OR an emergency use of a short course&#xD;
                  of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4&#xD;
                  days)&#xD;
&#xD;
               -  Autologous stem cell transplantation at least 12 weeks prior to starting study&#xD;
                  treatment&#xD;
&#xD;
               -  Allogeneic stem cell transplantation at least 24 weeks prior to starting&#xD;
                  treatment, and these subjects must also NOT have moderate to severe active acute&#xD;
                  or chronic graft versus host disease (GVHD)&#xD;
&#xD;
          -  Subjects with known chronic obstructive pulmonary disease (COPD) with a forced&#xD;
             expiratory volume in 1 second (FEV1) &lt; 50% of predicted normal&#xD;
&#xD;
          -  Subjects with grade 2 or higher residual toxicities from prior therapy (including&#xD;
             grade 2 or higher peripheral neuropathy or any grade neuropathy with pain) with the&#xD;
             exception of alopecia&#xD;
&#xD;
          -  Subjects who have undergone major surgery within 28 days of study day 1. NOTE:&#xD;
             Subjects with planned surgical procedures to be conducted under local anesthesia may&#xD;
             participate. Kyphoplasty or vertebroplasty are not considered major surgery&#xD;
&#xD;
          -  Subjects with central nervous system involvement of myeloma&#xD;
&#xD;
          -  Subjects with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection requiring intravenous antibiotics or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirements&#xD;
&#xD;
          -  Subjects with myocardial infarction within 6 months of study day 1, symptomatic&#xD;
             congestive heart failure (New York Heart Association [NYHA] class III and higher),&#xD;
             unstable angina, or uncontrolled cardiac arrhythmia (grade 2 or higher)&#xD;
&#xD;
          -  Subjects with gastrointestinal (GI) tract disease causing the inability to take oral&#xD;
             medication, malabsorption syndrome, requirement for intravenous alimentation, prior&#xD;
             surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g.,&#xD;
             Crohn's disease, ulcerative colitis)&#xD;
&#xD;
          -  Subjects with active hepatitis B or C virus infection, or known human immunodeficiency&#xD;
             virus (HIV) positive&#xD;
&#xD;
          -  Subjects diagnosed or treated for another malignancy within 2 years before study&#xD;
             enrollment or previously diagnosed with another malignancy and have any evidence of&#xD;
             residual disease. Subjects with nonmelanoma skin cancer or carcinoma in situ of any&#xD;
             type are not excluded if they have undergone complete resection&#xD;
&#xD;
          -  Female patients who are lactating or have a positive serum pregnancy test during the&#xD;
             screening period&#xD;
&#xD;
          -  Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days&#xD;
             will be considered a sufficient interval between treatment and administration of the&#xD;
             ixazomib&#xD;
&#xD;
          -  Participation in other clinical trials, including those with other investigational&#xD;
             agents not included in this trial, within 30 days of the start of this trial and&#xD;
             throughout the duration of this trial&#xD;
&#xD;
          -  Patients that have previously participated in a study with ixazomib whether treated&#xD;
             with ixazomib or not&#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>Hans C Lee</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hans Lee</last_name>
    <phone>713-792-2860</phone>
    <email>hclee@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hans C. Lee</last_name>
      <phone>713-745-8430</phone>
      <email>hclee@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Hans C. Lee</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>October 12, 2022</last_update_submitted>
  <last_update_submitted_qc>October 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2022</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>Bortezomib</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/NCT03763162
org study id: 2018-0512
secondary id: NCI-2018-02830
secondary id: 2018-0512
nct id: NCT03763162
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well daratumumab, bortezomib, and dexamethasone followed by
      daratumumab, ixazomib, and dexamethasone in treating patients with multiple myeloma that has
      come back (relapsed) or does not response to treatment (refractory). Immunotherapy with
      monoclonal antibodies, such as daratumumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in
      chemotherapy, such as 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. Bortezomib and ixazomib may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Giving daratumumab, bortezomib, and dexamethasone
      followed by daratumumab, ixazomib, and dexamethasone may work better and help to control
      cancer in patients with multiple myeloma.
PRIMARY OBJECTIVE:

      I. To evaluate the progression-free survival of subjects with daratumumab, bortezomib, and
      dexamethasone (DVd) treatment followed by daratumumab, ixazomib, and dexamethasone (DId)
      treatment.

      SECONDARY OBJECTIVES:

      I. To evaluate overall response rate (ORR) as assessed by International Myeloma Working Group
      Criteria (IMWG).

      II. To evaluate time to response (TTR). III. To evaluate time to progression (TTP). IV. To
      evaluate duration of response (DOR). V. To evaluate overall survival (OS). VI. To evaluate
      the safety and tolerability. VII. To evaluate minimal residual disease (MRD) rate. VIII. To
      evaluate quality of life (QoL) using the Treatment Satisfaction Questionnaire for Medication
      (TSMQ-9) and European Organization for the Research and Treatment of Cancer Quality of Life
      Questionnaire (EORTC QLQ-C30) patient reported questionnaires.

      EXPLORATORY OBJECTIVE:

      I. To evaluate biomarkers of response to treatment and mechanisms of resistance with
      pretreatment and post-treatment bone marrow and blood samples with deoxyribonucleic acid
      (DNA) and ribonucleic acid (RNA) sequencing and immune profiling by flow cytometry.

      OUTLINE:

      Patients receive daratumumab intravenously (IV) over 3.5-6.5 hours on days 1, 8, and 15,
      bortezomib subcutaneously (SC) on days 1, 4, 8, and 11, and dexamethasone IV over 15 minutes
      on days 1, 8, and 15 and orally (PO) on days 2, 4, 5, 9, 11, 12, and 16. Treatment repeats
      every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity.
      Patients then receive daratumumab IV over 3.5 hours on days 1 and 15 of cycles 4-7 and day 1
      of subsequent cycles, ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes
      or PO once weekly. Cycles repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study, patients are followed up at 30 days and then periodically for up
      to 24 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival (PFS)
time frame: From the date of first dose of any study drug treatment to the date of first documentation of progressive disease, or death due to any cause, whichever occurs first, assessed up to 18 months
description: Will be assessed by International Myeloma Working Group Criteria (IMWG).
arm group label: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)
arm group type: Experimental
description: Patients receive daratumumab IV over 3.5-6.5 hours on days 1, 8, and 15, bortezomib SC on days 1, 4, 8, and 11, and dexamethasone IV over 15 minutes on days 1, 8, and 15 and PO on days 2, 4, 5, 9, 11, 12, and 16. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive daratumumab IV over 3.5 hours on days 1 and 15 of cycles 4-7 and day 1 of subsequent cycles, ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO once weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Bortezomib
description: Given SC
arm group label: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)
other name: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
other name: LDP 341
other name: MLN341
other name: PS-341
other name: PS341
other name: Velcade
intervention type: Biological
intervention name: Daratumumab
description: Given IV
arm group label: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)
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 IV or PO
arm group label: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)
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: Baycadron
other name: Baycuten
other name: Baycuten N
other name: Cortidexason
other name: Cortisumman
other name: Decacort
other name: Decadrol
other name: Decadron
other name: Decadron DP
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: Dexamethasone Intensol
other name: Dexamethasonum
other name: Dexamonozon
other name: Dexapos
other name: Dexinoral
other name: Dexone
other name: Dinormon
other name: Dxevo
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: TaperDex
other name: Visumetazone
other name: ZoDex
intervention type: Drug
intervention name: Ixazomib
description: Given PO
arm group label: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)
other name: MLN-2238
other name: MLN2238
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)
other name: Quality of Life Assessment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hans C Lee
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Hans Lee
phone: 713-792-2860
email: hclee@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Bortezomib
mesh term: Daratumumab
mesh term: Ixazomib
mesh term: Ichthammol
mesh term: BB 1101
mesh term: Glycine