<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/NCT03748953</url>
  </required_header>
  <id_info>
    <org_study_id>C16021 CCS</org_study_id>
    <secondary_id>2014-001394-13</secondary_id>
    <nct_id>NCT03748953</nct_id>
    <nct_alias>NCT04371770</nct_alias>
  </id_info>
  <brief_title>Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Participants With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation (SCT)</brief_title>
  <official_title>China Continuation: A Single-Arm, Open-Label Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the long-term safety and tolerability of ixazomib&#xD;
      maintenance therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called ixazomib. Ixazomib is being tested to slow&#xD;
      disease progression and improve overall survival in Chinese participants who have newly&#xD;
      diagnosed multiple myeloma (NDMM) who have had a major positive response to initial therapy&#xD;
      and have not undergone stem cell transplantation (SCT). This study will look at the effect of&#xD;
      ixazomib has on the length of time that participants are free of disease progression and&#xD;
      their overall survival. After the implementation of Amendment 8, participants who received&#xD;
      placebo-matching capsules before unblinding and have not yet experienced disease progression&#xD;
      will cross over to receive ixazomib.&#xD;
&#xD;
      The study will enroll approximately 30 patients. Participants will be assigned to a single&#xD;
      treatment group&#xD;
&#xD;
      • Ixazomib&#xD;
&#xD;
      All participants will be asked to take one capsule on Days 1, 8, and 15 of every 28-day&#xD;
      cycle, for up to approximately 24 months (equivalent to 26 cycles [if no cycle delays], to&#xD;
      the nearest complete cycle) or until documented progressive disease (PD) or intolerable&#xD;
      toxicity, whichever occurs first.&#xD;
&#xD;
      This multi-center trial will be conducted in China. The overall time to participate in this&#xD;
      study is until a total of approximately up to 60 months. Participants will make multiple&#xD;
      visits to the clinic, and every 4 weeks until the next line of therapy begins for a follow-up&#xD;
      assessment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 24, 2019</start_date>
  <completion_date type="Anticipated">November 29, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 29, 2023</primary_completion_date>
  <phase>Phase 3</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>Number of Participants for Each of the Eastern Cooperative Oncology Group (ECOG) Performance Status</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after progressive disease (PD) until next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>ECOG performance status will assess participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (&gt;50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair &gt;50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants with Adverse Events (AEs)</measure>
    <time_frame>From the date of first dose of study drug through 30 days after last dose of study drug (approximately 25 months)</time_frame>
    <description>Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants with Serious Adverse Event (SAE)</measure>
    <time_frame>From the date of first dose through 30 days after last dose of study drug (approximately 25 months)</time_frame>
    <description>A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Any Markedly Abnormal Standard Safety Laboratory Values</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after progressive disease (PD) until next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>Clinical laboratory evaluations will be performed by a central laboratory. The number of participants with any markedly abnormal standard safety laboratory values collected throughout study will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks until PD or death from any cause (approximately 60 months)</time_frame>
    <description>PFS is defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator or death from any cause, whichever occurs first. PD is defined as &gt;=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved free light chain (FLC) levels (absolute increase &gt;10 mg/dL); bone marrow plasma cell percent &gt;/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From the date of first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurs later (approximately 60 months)</time_frame>
    <description>OS is measured as the time from the date of first dose of study drug to the date of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants who Achieve or Maintain Best Response Before PD or up to Subsequent Therapy</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>Response will be assessed as per the International Myeloma Working Group (IMWG) criteria. Best response will include partial responses (PR), very good partial response (VGPR) and complete response (CR). PR is defined as &gt;=50% reduction of serum M-component, urinary M- component by &gt;=90% to &lt;200 mg/24-hour reduction; &gt;=50% in the difference between involved and uninvolved FLC; bone marrow plasma cells (PC) &gt;/=30%; reduction &gt;/=50% reduction in the soft tissue size. VGPR is defined as serum or urine M-component detectable by immunofixation but not on electrophoresis; &gt;=90% reduction in serum or urine M-component level &lt;100 mg/24 hour. CR is defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; &lt;5% PCs in bone marrow.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Complete Response (CR)</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>Duration of CR is defined as the time from the date of first dose of study drug or the date of CR to the date of first documentation of PD. CR is defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; &lt;5% PCs in bone marrow.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP)</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>TTP is defined as the time from the date of first dose of study drug to the date of first documentation of PD. PD is defined as &gt;=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved FLC levels (absolute increase &gt;10 mg/dL); bone marrow plasma cell percent &gt;/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Next-Line Therapy (TTNT)</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>TTNT is defined as the time from the date of first dose of study drug to the date of the first dose of next-line of antineoplastic therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With A New Primary Malignancy</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause or termination of the study (approximately 60 months)</time_frame>
    <description>Percentage of participants with a new primary malignancy will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30</measure>
    <time_frame>From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)</time_frame>
    <description>The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1=not at all (best) to 4=very much (worst) and 2 questions answered on a 7-point scale where 1=very poor (worst) to 7= excellent (best).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation Between Frailty Status and PFS and OS</measure>
    <time_frame>From the date of first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurs later (approximately 60 months)</time_frame>
    <description>Participants frailty status will be assessed on basis of 4 components: age(&lt;75, 75- 80, and&gt;80 years correspond to frailty scores of 0, 1, and 2, respectively), Charlson comorbidity scoring system without age weighting (scores of ≤ 1 and ≥ 2 correspond to frailty scores of 0 and 1, respectively), Katz index of independence in activities of daily living (scores of &gt;4 and ≤4 correspond to frailty scores of 0 and 1, respectively) and Lawton instrumental activities of daily living scale (scores of &gt;5 and ≤5 correspond to frailty scores of 0 and 1, respectively). The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator. OS will be measured as the time from the date of first dose of study drug to the date of death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Ixazomib</measure>
    <time_frame>Cycle1 Day1(1,4 hours post-dose),pre-dose Cycle1 on Days8 and 15;pre-dose Cycle2 on Days1 and 8;pre-dose Cycles 3-5 on Day1;pre-dose Cycle5 on Day8(only for those who have dose escalated after Cycle4); pre-dose Cycles 6-10 on Day 1;each cycle of 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Resolution of Peripheral Neuropathy (PN) Events</measure>
    <time_frame>From the date of first dose of study drug to next-line therapy or 6 months after PD (approximately 60 months)</time_frame>
    <description>PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution is defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Improvement of PN Events</measure>
    <time_frame>From the date of first dose of study drug to next-line therapy or 6 months after PD (approximately 60 months)</time_frame>
    <description>PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the MedDRA. A PN event is considered to be improved if the event improves from the maximum grade; that is, all the grades recorded after the maximum grade are less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Ixazomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ixazomib 3 mg, capsules, orally, once on Days 1, 8 and 15 of every 28-day cycle for Cycle 1 through Cycle 4, during which if the participants have tolerated the initial dose, the dose may be escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8 and 15 of every 28-day cycle for Cycle 5 through Cycle 26, or until documented PD or intolerable toxicity, whichever occurs first.&#xD;
Participants who received placebo-matching capsules before unblinding and have not yet experienced disease progression will have the opportunity to cross over to ixazomib maintenance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixazomib</intervention_name>
    <description>Ixazomib Capsules</description>
    <arm_group_label>Ixazomib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult male or female participants aged 18 years or older with a confirmed diagnosis of&#xD;
             symptomatic NDMM according to standard criteria.&#xD;
&#xD;
          2. Has completed 6 to 12 months (±2 weeks) of initial therapy, during which the&#xD;
             participant was treated to best response, defined as the best response maintained for&#xD;
             2 cycles after the M-protein nadir is reached.&#xD;
&#xD;
          3. Has documented major response (partial response [PR], very good partial response&#xD;
             [VGPR], complete response [CR]) according to the international myeloma working group&#xD;
             (IMWG) uniform response criteria, version 2011, after this initial therapy.&#xD;
&#xD;
          4. Female participants who:&#xD;
&#xD;
             Are postmenopausal for at least 1 year before the screening visit, OR Are surgically&#xD;
             sterile, OR If they are of childbearing potential, agree to practice 2 effective&#xD;
             methods of contraception, at the same time, from the time of signing the informed&#xD;
             consent through 90 days after the last dose of study drug, or Agree to practice true&#xD;
             abstinence, when this is in line with the preferred and usual lifestyle of the&#xD;
             participant. (Periodic abstinence [e.g., calendar, ovulation,symptothermal,&#xD;
             postovulation methods] and withdrawal are not acceptable methods of contraception.)&#xD;
&#xD;
             Male participants, even if surgically sterilized (i.e., status postvasectomy), who:&#xD;
&#xD;
             Agree to practice effective barrier contraception during the entire study Treatment&#xD;
             period and through 90 days after the last dose of study drug, or Agree to practice&#xD;
             true abstinence, when this is in line with the preferred and usual lifestyle of the&#xD;
             participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal,&#xD;
             postovulation methods for the female partner] and withdrawal are not acceptable&#xD;
             methods of contraception.)&#xD;
&#xD;
          5. Voluntary written consent must be given before performance of any study-related&#xD;
             procedure not part of standard medical care, with the understanding that consent may&#xD;
             be withdrawn by the participant at any time without prejudice to future medical care.&#xD;
&#xD;
          6. Has availability of complete documentation for:&#xD;
&#xD;
               1. Details of initial disease state, initial therapy, and response&#xD;
&#xD;
               2. Cytogenetic assessment at diagnosis (cytogenetic assessment performed after&#xD;
                  diagnosis must be approved by a Takeda project clinician or designee)&#xD;
&#xD;
               3. International Staging System (ISS) staging at diagnosis (requiring beta&#xD;
                  2-microglobulin and serum albumin results).&#xD;
&#xD;
          7. Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.&#xD;
&#xD;
          8. Suitable venous access for the study-required blood sampling and consent for the&#xD;
             specific amounts that will be taken.&#xD;
&#xD;
          9. Participant is willing and able to adhere to the study visit schedule and other&#xD;
             protocol requirements including blood sampling and bone marrow aspiration.&#xD;
&#xD;
         10. Participants must meet the following clinical laboratory criteria at study entry:&#xD;
&#xD;
        1. Absolute neutrophil count (ANC) ≥1,000/mm^3 without growth factor support and platelet&#xD;
        count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria&#xD;
        are not allowed within 3 days before enrollment.&#xD;
&#xD;
        2. Total bilirubin ≤1.5*the upper limit of the normal range (ULN). 3. Alanine&#xD;
        aminotransferase and aspartate aminotransferase ≤3*ULN. 4. Calculated creatinine clearance&#xD;
        ≥30 mL/min (using the Cockroft-Gault equation).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has multiple myeloma that relapsed after, or was not responsive to, initial therapy.&#xD;
&#xD;
          2. Had prior stem-cell transplantation (SCT).&#xD;
&#xD;
          3. Has radiotherapy within 14 days before enrollment.&#xD;
&#xD;
          4. Had been diagnosed or treated for another malignancy within 5 years before enrollment&#xD;
             or previously diagnosed with another malignancy with evidence of residual disease.&#xD;
             Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not&#xD;
             excluded if they have undergone complete resection.&#xD;
&#xD;
          5. Female participants who are lactating and breastfeeding or have a positive serum&#xD;
             pregnancy test during the Screening period.&#xD;
&#xD;
          6. Has major surgery within 14 days before enrollment.&#xD;
&#xD;
          7. Has central nervous system involvement.&#xD;
&#xD;
          8. Infection requiring intravenous (IV) antibiotic therapy or other serious infection&#xD;
             within 14 days before enrollment.&#xD;
&#xD;
          9. Has diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell&#xD;
             leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative&#xD;
             syndrome.&#xD;
&#xD;
         10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled&#xD;
             hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure,&#xD;
             unstable angina, or myocardial infarction within the past 6 months.&#xD;
&#xD;
         11. Systemic treatment with strong cytochrome P450 (CYP3A) inducers (rifampin,&#xD;
             rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's&#xD;
             wort within 14 days before enrollment.&#xD;
&#xD;
         12. Ongoing or active infection, known human immunodeficiency virus positive, active&#xD;
             hepatitis B or C infection.&#xD;
&#xD;
         13. Has comorbid systemic illnesses or other severe concurrent disease that, in the&#xD;
             judgment of the investigator, would make the participant inappropriate for entry into&#xD;
             this study or interfere significantly with the proper assessment of safety and&#xD;
             toxicity of the prescribed regimens (e.g., peripheral neuropathy (PN) that is Grade 1&#xD;
             with pain or Grade 2 or higher of any cause).&#xD;
&#xD;
         14. Psychiatric illness/social situation that would limit compliance with study&#xD;
             requirements.&#xD;
&#xD;
         15. Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
             various formulations of any agent.&#xD;
&#xD;
         16. Inability to swallow oral medication, inability or unwillingness to comply with the&#xD;
             drug administration requirements, or gastrointestinal (GI) procedure that could&#xD;
             interfere with the oral absorption or tolerance of treatment.&#xD;
&#xD;
         17. Treatment with any investigational products within 30 days before enrollment.&#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>Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Takeda</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Chaoyang Hospital Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University Third Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100191</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tongji Hospital Tongji Medical College Huazhong University of Science and Technology</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shengjing Hospital of China Medical University</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <zip>110004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Renji Hospital Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Chang Zheng Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruijin Hospital Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1st Affiliated Hospital of Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.takeda.com/study-detail/5f6b603a4db2bf003ab4a2b7?idFilter=%5B%22C16021CSC%22%5D</url>
    <description>To obtain more information about this study, click this link.</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 16, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>March 30, 2023</last_update_submitted>
  <last_update_submitted_qc>March 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug Therapy</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ixazomib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_access_criteria>IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/takeda/</ipd_url>
  </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/NCT03748953
org study id: C16021 CCS
secondary id: 2014-001394-13
nct id: NCT03748953
nct alias: NCT04371770
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the long-term safety and tolerability of ixazomib
      maintenance therapy.
The drug being tested in this study is called ixazomib. Ixazomib is being tested to slow
      disease progression and improve overall survival in Chinese participants who have newly
      diagnosed multiple myeloma (NDMM) who have had a major positive response to initial therapy
      and have not undergone stem cell transplantation (SCT). This study will look at the effect of
      ixazomib has on the length of time that participants are free of disease progression and
      their overall survival. After the implementation of Amendment 8, participants who received
      placebo-matching capsules before unblinding and have not yet experienced disease progression
      will cross over to receive ixazomib.

      The study will enroll approximately 30 patients. Participants will be assigned to a single
      treatment group

      • Ixazomib

      All participants will be asked to take one capsule on Days 1, 8, and 15 of every 28-day
      cycle, for up to approximately 24 months (equivalent to 26 cycles [if no cycle delays], to
      the nearest complete cycle) or until documented progressive disease (PD) or intolerable
      toxicity, whichever occurs first.

      This multi-center trial will be conducted in China. The overall time to participate in this
      study is until a total of approximately up to 60 months. Participants will make multiple
      visits to the clinic, and every 4 weeks until the next line of therapy begins for a follow-up
      assessment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants for Each of the Eastern Cooperative Oncology Group (ECOG) Performance Status
time frame: From the date of first dose of study drug to every 4 weeks after progressive disease (PD) until next line therapy or death from any cause (approximately 60 months)
description: ECOG performance status will assess participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead.
measure: Percentage of Participants with Adverse Events (AEs)
time frame: From the date of first dose of study drug through 30 days after last dose of study drug (approximately 25 months)
description: Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug.
measure: Percentage of Participants with Serious Adverse Event (SAE)
time frame: From the date of first dose through 30 days after last dose of study drug (approximately 25 months)
description: A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
measure: Number of Participants with Any Markedly Abnormal Standard Safety Laboratory Values
time frame: From the date of first dose of study drug to every 4 weeks after progressive disease (PD) until next line therapy or death from any cause (approximately 60 months)
description: Clinical laboratory evaluations will be performed by a central laboratory. The number of participants with any markedly abnormal standard safety laboratory values collected throughout study will be reported.
measure: Progression-Free Survival (PFS)
time frame: From the date of first dose of study drug to every 4 weeks until PD or death from any cause (approximately 60 months)
description: PFS is defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator or death from any cause, whichever occurs first. PD is defined as >=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); bone marrow plasma cell percent >/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.
measure: Overall Survival (OS)
time frame: From the date of first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurs later (approximately 60 months)
description: OS is measured as the time from the date of first dose of study drug to the date of death.
measure: Percentage of Participants who Achieve or Maintain Best Response Before PD or up to Subsequent Therapy
time frame: From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)
description: Response will be assessed as per the International Myeloma Working Group (IMWG) criteria. Best response will include partial responses (PR), very good partial response (VGPR) and complete response (CR). PR is defined as >=50% reduction of serum M-component, urinary M- component by >=90% to <200 mg/24-hour reduction; >=50% in the difference between involved and uninvolved FLC; bone marrow plasma cells (PC) >/=30%; reduction >/=50% reduction in the soft tissue size. VGPR is defined as serum or urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum or urine M-component level <100 mg/24 hour. CR is defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; <5% PCs in bone marrow.
measure: Duration of Complete Response (CR)
time frame: From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)
description: Duration of CR is defined as the time from the date of first dose of study drug or the date of CR to the date of first documentation of PD. CR is defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; <5% PCs in bone marrow.
measure: Time to Progression (TTP)
time frame: From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)
description: TTP is defined as the time from the date of first dose of study drug to the date of first documentation of PD. PD is defined as >=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); bone marrow plasma cell percent >/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.
measure: Time to Next-Line Therapy (TTNT)
time frame: From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)
description: TTNT is defined as the time from the date of first dose of study drug to the date of the first dose of next-line of antineoplastic therapy.
measure: Percentage of Participants With A New Primary Malignancy
time frame: From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause or termination of the study (approximately 60 months)
description: Percentage of participants with a new primary malignancy will be reported.
measure: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30
time frame: From the date of first dose of study drug to every 4 weeks after PD or next line therapy or death from any cause (approximately 60 months)
description: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1=not at all (best) to 4=very much (worst) and 2 questions answered on a 7-point scale where 1=very poor (worst) to 7= excellent (best).
measure: Correlation Between Frailty Status and PFS and OS
time frame: From the date of first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurs later (approximately 60 months)
description: Participants frailty status will be assessed on basis of 4 components: age(<75, 75- 80, and>80 years correspond to frailty scores of 0, 1, and 2, respectively), Charlson comorbidity scoring system without age weighting (scores of ≤ 1 and ≥ 2 correspond to frailty scores of 0 and 1, respectively), Katz index of independence in activities of daily living (scores of >4 and ≤4 correspond to frailty scores of 0 and 1, respectively) and Lawton instrumental activities of daily living scale (scores of >5 and ≤5 correspond to frailty scores of 0 and 1, respectively). The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator. OS will be measured as the time from the date of first dose of study drug to the date of death.
measure: Plasma Concentration of Ixazomib
time frame: Cycle1 Day1(1,4 hours post-dose),pre-dose Cycle1 on Days8 and 15;pre-dose Cycle2 on Days1 and 8;pre-dose Cycles 3-5 on Day1;pre-dose Cycle5 on Day8(only for those who have dose escalated after Cycle4); pre-dose Cycles 6-10 on Day 1;each cycle of 28 days
measure: Time to Resolution of Peripheral Neuropathy (PN) Events
time frame: From the date of first dose of study drug to next-line therapy or 6 months after PD (approximately 60 months)
description: PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution is defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.
measure: Time to Improvement of PN Events
time frame: From the date of first dose of study drug to next-line therapy or 6 months after PD (approximately 60 months)
description: PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the MedDRA. A PN event is considered to be improved if the event improves from the maximum grade; that is, all the grades recorded after the maximum grade are less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.
arm group label: Ixazomib
arm group type: Experimental
description: Ixazomib 3 mg, capsules, orally, once on Days 1, 8 and 15 of every 28-day cycle for Cycle 1 through Cycle 4, during which if the participants have tolerated the initial dose, the dose may be escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8 and 15 of every 28-day cycle for Cycle 5 through Cycle 26, or until documented PD or intolerable toxicity, whichever occurs first.
Participants who received placebo-matching capsules before unblinding and have not yet experienced disease progression will have the opportunity to cross over to ixazomib maintenance.
intervention type: Drug
intervention name: Ixazomib
description: Ixazomib Capsules
arm group label: Ixazomib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Study Director
role: Study Director
affiliation: Takeda
facility: 
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country: China
url: https://clinicaltrials.takeda.com/study-detail/5f6b603a4db2bf003ab4a2b7?idFilter=%5B%22C16021CSC%22%5D
description: To obtain more information about this study, click this link.
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Ixazomib
sharing ipd: Yes
ipd description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd access criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
ipd url: https://vivli.org/ourmember/takeda/