<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/NCT01718743</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0277</org_study_id>
    <secondary_id>NCI-2012-02873</secondary_id>
    <secondary_id>2012-0277</secondary_id>
    <secondary_id>P30CA016672</secondary_id>
    <nct_id>NCT01718743</nct_id>
  </id_info>
  <brief_title>Ixazomib Citrate and Lenalidomide After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma</brief_title>
  <official_title>Phase II Study of the Combination of MLN 9708 With Lenalidomide as Maintenance Therapy Post Autologous Stem Cell Transplant in Patients With Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</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 ixazomib citrate and lenalidomide after stem cell&#xD;
      transplant 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;
      Biological therapies, such as lenalidomide, may stimulate the immune system in different ways&#xD;
      and stop cancer cells from growing. Giving ixazomib citrate together with lenalidomide may be&#xD;
      effective in treating multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Establish safety and efficacy of oral ixazomib citrate (MLN 9708) and lenalidomide in the&#xD;
      maintenance setting post autologous stem cell transplant (ASCT) in myeloma patients.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Incidence of secondary primary malignancy. II. Evaluate the best response rate (stringent&#xD;
      complete response [sCR]/near complete response [nCR]/very good partial response&#xD;
      [VGPR]/partial response [PR]).&#xD;
&#xD;
      III. Evaluate time to progression. IV. Evaluate time to next therapy. V. Evaluate the&#xD;
      tolerability and toxicity. VI. Evaluate M. D. Anderson Symptom Inventory (MDASI)-myeloma&#xD;
      symptom evaluation.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Beginning 60-180 days post-transplant, patients receive ixazomib citrate orally (PO) on days&#xD;
      1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 3, 2012</start_date>
  <completion_date type="Actual">April 12, 2023</completion_date>
  <primary_completion_date type="Actual">April 12, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Time from autologous stem cell transplant (ASCT) to time of clinical progression or death or the time of last contact, assessed up to 30 days after completion of study treatment</time_frame>
    <description>Monitored using the method of Thall et al. Estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>28 days</time_frame>
    <description>Toxicity data will be summarized by frequency tables.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best response rate (stringent complete response [sCR]/near complete response [nCR]/very good partial response [VGPR]/partial response [PR])</measure>
    <time_frame>Up to 30 days after completion of study treatment</time_frame>
    <description>Estimated along with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related unmanageable toxicities, including grade 3 non-hematologic effects, or grade 4 hematologic effects</measure>
    <time_frame>Up to 30 days after completion of study treatment</time_frame>
    <description>Toxicity data will be summarized by frequency tables.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of new primary malignancy</measure>
    <time_frame>Up to 30 days after completion of study treatment</time_frame>
    <description>Estimated along with 95% confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 30 days after completion of study treatment</time_frame>
    <description>Estimated using the Kaplan-Meier method. Cox proportional hazards model will be used to include multiple covariates. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>M. D. Anderson Symptom Inventory (MDASI)-myeloma symptom evaluation</measure>
    <time_frame>Up to 30 days after completion of study treatment</time_frame>
    <description>Analyzed with descriptive analysis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">83</enrollment>
  <condition>Hematopoietic Cell Transplantation Recipient</condition>
  <condition>Plasma Cell Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (ixazomib citrate, lenalidomide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Beginning 60-180 days post-transplant, patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ixazomib Citrate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ixazomib citrate, lenalidomide)</arm_group_label>
    <other_name>MLN-9708</other_name>
    <other_name>MLN9708</other_name>
    <other_name>Ninlaro</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ixazomib citrate, lenalidomide)</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 citrate, lenalidomide)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must have undergone autologous stem cell transplantation, with melphalan as a&#xD;
             preparative regimen, within 12 months of initiation of induction therapy for newly&#xD;
             diagnosed myeloma&#xD;
&#xD;
          -  Time to initiation of maintenance therapy; patients may start maintenance therapy as&#xD;
             early as 60 days post-transplant and up to 180 days post-transplant; as long as they&#xD;
             meet the following criteria:&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3; platelet transfusions to help patients meet&#xD;
             eligibility criteria are not allowed within 3 days before study enrollment&#xD;
&#xD;
          -  Neutrophil count &gt;= 1000/mm^3; (no growth factors within 5 days prior to first dose of&#xD;
             the study drug)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x ULN&#xD;
&#xD;
          -  Creatinine &lt; 2.5 mg/dL&#xD;
&#xD;
          -  Recovered (i.e., =&lt; grade 1 toxicity) from the reversible effects of autologous stem&#xD;
             cell transplant&#xD;
&#xD;
          -  Patients whose primary therapy was changed due to suboptimal response of toxicity will&#xD;
             be eligible, however no more than 2 regimens will be allowed prior to ASCT&#xD;
&#xD;
          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 to 2&#xD;
&#xD;
          -  Voluntary written informed consent before performance of any study-related procedure&#xD;
             not part of normal medical care, with the understanding that consent may be withdrawn&#xD;
             by the subject at any time without prejudice to future medical care&#xD;
&#xD;
          -  Female patients who: are postmenopausal for at least 1 year before the screening&#xD;
             visit, OR are surgically sterile, OR if they are childbearing potential, agree to&#xD;
             practice 2 effective methods of contraception, at the same time, from the time of&#xD;
             signing the informed consent, during study treatment and for 90 days after the last&#xD;
             dose of study treatment, AND&#xD;
&#xD;
               -  Must also adhere to guidelines of any treatment-specific pregnancy prevention&#xD;
                  program, if applicable, OR&#xD;
&#xD;
               -  Agree to practice true abstinence when this is in line with the preferred and&#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 patients, even if surgically sterilized (i.e., status post vasectomy), must agree&#xD;
             to one of the following: agree to practice effective barrier contraception during the&#xD;
             entire study treatment period and through 90 days after the last dose of study&#xD;
             treatment, OR&#xD;
&#xD;
               -  Must also adhere to guidelines of any treatment-specific pregnancy prevention&#xD;
                  program, if applicable, OR&#xD;
&#xD;
               -  Agree to practice true abstinence when this is in line with the preferred and&#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;
          -  Patient has &gt;= grade 3 peripheral neuropathy, or grade 2 with pain on clinical&#xD;
             examination during the screening period&#xD;
&#xD;
          -  Major surgery within 14 days before the first dose of study drug&#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;
             MLN9708&#xD;
&#xD;
          -  Known active central nervous system involvement&#xD;
&#xD;
          -  Systemic treatment, within 14 days before study enrollment, with strong inhibitors of&#xD;
             CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), CYP3A (clarithromycin, telithromycin,&#xD;
             itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A&#xD;
             inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital),&#xD;
             or use of Ginkgo biloba or St. John's wort&#xD;
&#xD;
          -  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;
          -  Evidence of current uncontrolled cardiovascular conditions, including uncontrolled&#xD;
             hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,&#xD;
             unstable angina, or myocardial infarction within the past 6 months&#xD;
&#xD;
          -  Female subject who are lactating or have a positive serum pregnancy test during the&#xD;
             screening period&#xD;
&#xD;
          -  Serious medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with participation or completion of treatment according to this&#xD;
             protocol&#xD;
&#xD;
          -  Corrected QT interval using Bazett's formula (QTcB) &gt; 470 milliseconds (msec) on a&#xD;
             12-lead electrocardiogram (ECG) obtained during the screening period; if a machine&#xD;
             reading is above this value, the ECG should be reviewed by a qualified reader and&#xD;
             confirmed on a subsequent ECG&#xD;
&#xD;
          -  Ongoing or active systemic infection, known human immunodeficiency virus (HIV)&#xD;
             positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus&#xD;
             hepatitis&#xD;
&#xD;
          -  Infection requiring systemic antibiotic therapy or other serious infection within 14&#xD;
             days before study enrollment&#xD;
&#xD;
          -  Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
             various formulations&#xD;
&#xD;
          -  Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment&#xD;
             of the investigator, would make the patient inappropriate for entry into this study or&#xD;
             interfere significantly with the proper assessment of safety and toxicity of the&#xD;
             prescribed regimens&#xD;
&#xD;
          -  Diagnosed or treated for another malignancy within 2 years before study enrollment or&#xD;
             previously diagnosed with another malignancy and have any evidence of residual&#xD;
             disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are&#xD;
             not excluded if they have undergone complete resection&#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>Krina Patel</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 29, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 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>Lenalidomide</mesh_term>
    <mesh_term>Ixazomib</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/NCT01718743
org study id: 2012-0277
secondary id: NCI-2012-02873
secondary id: 2012-0277
secondary id: P30CA016672
nct id: NCT01718743
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well ixazomib citrate and lenalidomide after stem cell
      transplant 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.
      Biological therapies, such as lenalidomide, may stimulate the immune system in different ways
      and stop cancer cells from growing. Giving ixazomib citrate together with lenalidomide may be
      effective in treating multiple myeloma.
PRIMARY OBJECTIVES:

      I. Establish safety and efficacy of oral ixazomib citrate (MLN 9708) and lenalidomide in the
      maintenance setting post autologous stem cell transplant (ASCT) in myeloma patients.

      SECONDARY OBJECTIVES:

      I. Incidence of secondary primary malignancy. II. Evaluate the best response rate (stringent
      complete response [sCR]/near complete response [nCR]/very good partial response
      [VGPR]/partial response [PR]).

      III. Evaluate time to progression. IV. Evaluate time to next therapy. V. Evaluate the
      tolerability and toxicity. VI. Evaluate M. D. Anderson Symptom Inventory (MDASI)-myeloma
      symptom evaluation.

      OUTLINE:

      Beginning 60-180 days post-transplant, patients receive ixazomib citrate orally (PO) on days
      1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: Time from autologous stem cell transplant (ASCT) to time of clinical progression or death or the time of last contact, assessed up to 30 days after completion of study treatment
description: Monitored using the method of Thall et al. Estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
measure: Incidence of adverse events
time frame: 28 days
description: Toxicity data will be summarized by frequency tables.
measure: Best response rate (stringent complete response [sCR]/near complete response [nCR]/very good partial response [VGPR]/partial response [PR])
time frame: Up to 30 days after completion of study treatment
description: Estimated along with 95% confidence intervals.
measure: Treatment-related unmanageable toxicities, including grade 3 non-hematologic effects, or grade 4 hematologic effects
time frame: Up to 30 days after completion of study treatment
description: Toxicity data will be summarized by frequency tables.
measure: Incidence of new primary malignancy
time frame: Up to 30 days after completion of study treatment
description: Estimated along with 95% confidence intervals.
measure: Overall survival
time frame: Up to 30 days after completion of study treatment
description: Estimated using the Kaplan-Meier method. Cox proportional hazards model will be used to include multiple covariates. Log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
measure: M. D. Anderson Symptom Inventory (MDASI)-myeloma symptom evaluation
time frame: Up to 30 days after completion of study treatment
description: Analyzed with descriptive analysis.
arm group label: Treatment (ixazomib citrate, lenalidomide)
arm group type: Experimental
description: Beginning 60-180 days post-transplant, patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Ixazomib Citrate
description: Given PO
arm group label: Treatment (ixazomib citrate, lenalidomide)
other name: MLN-9708
other name: MLN9708
other name: Ninlaro
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Treatment (ixazomib citrate, lenalidomide)
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 citrate, lenalidomide)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Krina Patel
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Lenalidomide
mesh term: Ixazomib
mesh term: Glycine