<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/NCT02986451</url>
  </required_header>
  <id_info>
    <org_study_id>MM-2016</org_study_id>
    <nct_id>NCT02986451</nct_id>
  </id_info>
  <brief_title>Clarithromycin,Lenalidomide and Dexamethasone for Relapsed/Refractory Myeloma</brief_title>
  <official_title>Efficacy and Safety Study of BiRD (Biaxin [Clarithromycin]/Revlimid [Lenalidomide]/Dexamethasone) Combination Therapy in Relapsed/Refractory Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>China Food and Drug Administration</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II study investigating the efficacy and safety of a combination of&#xD;
      biaxin,lenalidomide and dexamethasone in subjects with relapsed/refractory MM.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The combination of lenalidomide and dexamethasone is effective in increasing the response&#xD;
      rate, time to progression, and overall survival in patients with relapsed or refractory&#xD;
      myeloma.Clarithromycin is an antibiotic that has shown efficacy in association with steroids&#xD;
      and lenalidomide.Clarithromycin, lenalidomide and dexamethasone (BiRd) in newly diagnosed MM&#xD;
      has yielded an overall response rates (ORR) of 93% and a progression-free survival (PFS) of&#xD;
      43 months.No prospective study of BiRd to treat relapsed or refractory myeloma has been&#xD;
      reported so far.The goal of this phase 2 clinical trial was to assess the response rate and&#xD;
      toxicity of a combination regimen of clarithromycin (Biaxin), lenalidomide (Revlimid), and&#xD;
      dexamethasone (BiRD) for the treatment of relapsed/refractory MM.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</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>Overall Response Rate (ORR)</measure>
    <time_frame>30 months</time_frame>
    <description>ORR is defined as the proportion of patients with CR, nCR or partial response (PR) based on modified EBMT criteria per investigator assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>30 months</time_frame>
    <description>PFS, defined as time from first dose of study treatment to progression or death due to any cause, as assessed by investigator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>30 months</time_frame>
    <description>OS, defined as time from first dose of study treatment to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of combination therapy assessed using the National Cancer institute-Common Toxicology Criteria (NCI-CTC) grade scale for AEs and Lab assessments</measure>
    <time_frame>30 months</time_frame>
    <description>Safety of combination therapy (Clarithromycin,lenalidomide and dexamethasone) as assessed by toxicity, which will be assessed using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale for Adverse Events and for laboratory assessments (v4.03) that include biochemistry, hematology, urinalysis; special safety assessments that include LVEF, Thyroid function Creatinine clearance and ECGs (electrocardiograms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genomic Predictors of Response Rate and PFS</measure>
    <time_frame>30 months</time_frame>
    <description>Blood (about 1-2 tablespoons) collected for biomarker and routine tests and to evaluate the ORR and PFS.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Relapse/Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients received clarithromycin, lenalidomide, and dexamethasone in 28-day cycles. Dexamethasone (40 mg) was given orally on days 1, 8, 15, and 22. Clarithromycin (500 mg) was given orally twice daily.Lenalidomide (25 mg) was given orally daily on days 1 to 21</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>clarithromycin</intervention_name>
    <description>Clarithromycin 500mg PO twice daily on days 1-28 for a 28-day cycle.</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Biaxin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle.</description>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>hexadecadrol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient has a previous diagnosis of multiple myeloma&#xD;
&#xD;
          -  Patient requires retreatment for multiple myeloma&#xD;
&#xD;
          -  Subject has measurable disease as defined by &gt; 0.5 g/dL serum monoclonal protein, &gt;10&#xD;
             mg/dL involved serum free light chain (either kappa or lambda) provided that the serum&#xD;
             free light chain ratio is abnormal, &gt;0.2 g/24 hrs urinary M-protein excretion, and/or&#xD;
             measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either&#xD;
             CT scanning or MRI&#xD;
&#xD;
          -  Subject has a Karnofsky performance status ≥60% (&gt;50% if due to bony involvement of&#xD;
             myeloma (see Appendix IV)&#xD;
&#xD;
          -  Subject has a life expectancy ≥ 3 months&#xD;
&#xD;
          -  Subjects must meet the following laboratory parameters:&#xD;
&#xD;
        Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) Hemoglobin ≥ 7 g/dL Platelet&#xD;
        count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration) Serum SGOT/AST &lt;3.0 x&#xD;
        upper limits of normal (ULN) Serum SGPT/ALT &lt;3.0 x upper limits of normal (ULN) Serum total&#xD;
        bilirubin &lt;2.0 mg/dL (34 µmol/L) Creatinine clearance ≥ 30 cc/min&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has immeasurable MM (no measurable monoclonal protein, free light chains in&#xD;
             blood or urine, or measureable plasmacytoma on radiologic scanning)&#xD;
&#xD;
          -  Subject has a prior history of other malignancies unless disease-free for ≥ 5 years,&#xD;
             except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the&#xD;
             cervix or breast, or localized prostate cancer with Gleason score &lt; 7 with stable&#xD;
             prostate specific antigen (PSA) levels&#xD;
&#xD;
          -  Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA&#xD;
             (New York Hospital Association) Class III or IV heart failure (see Appendix VI),&#xD;
             Ejection Fraction &lt; 35%, uncontrolled angina, severe uncontrolled ventricular&#xD;
             arrhythmias, electrocardiographic evidence of acute ischemia or active conduction&#xD;
             system abnormalities&#xD;
&#xD;
          -  Female subject who is pregnant or lactating&#xD;
&#xD;
          -  Subject has known HIV infection&#xD;
&#xD;
          -  Subject has known active hepatitis B or hepatitis C infection&#xD;
&#xD;
          -  Subject has active viral or bacterial infections or any coexisting medical problem&#xD;
             that would significantly increase the risks of this treatment program&#xD;
&#xD;
          -  Subject is unable to reliably take oral medications&#xD;
&#xD;
          -  Subject has known hypersensitivity to dexamethasone,cyclophosphamide,paclitaxel&#xD;
&#xD;
          -  Subject has a history of thromboembolic event within the past 4 weeks prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Subject has any clinically significant medical or psychiatric disease or condition&#xD;
             that, in the investigator's opinion, may interfere with protocol adherence or a&#xD;
             subject's ability to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>zhongjun xia, MD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>hematological oncology department</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>GuangZhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>August 11, 2018</last_update_submitted>
  <last_update_submitted_qc>August 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>wanghua</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </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>Clarithromycin</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02986451
org study id: MM-2016
nct id: NCT02986451
lead sponsor: 
collaborator: 
has dmc: No
This phase II study investigating the efficacy and safety of a combination of
      biaxin,lenalidomide and dexamethasone in subjects with relapsed/refractory MM.
The combination of lenalidomide and dexamethasone is effective in increasing the response
      rate, time to progression, and overall survival in patients with relapsed or refractory
      myeloma.Clarithromycin is an antibiotic that has shown efficacy in association with steroids
      and lenalidomide.Clarithromycin, lenalidomide and dexamethasone (BiRd) in newly diagnosed MM
      has yielded an overall response rates (ORR) of 93% and a progression-free survival (PFS) of
      43 months.No prospective study of BiRd to treat relapsed or refractory myeloma has been
      reported so far.The goal of this phase 2 clinical trial was to assess the response rate and
      toxicity of a combination regimen of clarithromycin (Biaxin), lenalidomide (Revlimid), and
      dexamethasone (BiRD) for the treatment of relapsed/refractory MM.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR)
time frame: 30 months
description: ORR is defined as the proportion of patients with CR, nCR or partial response (PR) based on modified EBMT criteria per investigator assessment
measure: Progression Free Survival (PFS)
time frame: 30 months
description: PFS, defined as time from first dose of study treatment to progression or death due to any cause, as assessed by investigator
measure: Overall survival (OS)
time frame: 30 months
description: OS, defined as time from first dose of study treatment to death
measure: Safety of combination therapy assessed using the National Cancer institute-Common Toxicology Criteria (NCI-CTC) grade scale for AEs and Lab assessments
time frame: 30 months
description: Safety of combination therapy (Clarithromycin,lenalidomide and dexamethasone) as assessed by toxicity, which will be assessed using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale for Adverse Events and for laboratory assessments (v4.03) that include biochemistry, hematology, urinalysis; special safety assessments that include LVEF, Thyroid function Creatinine clearance and ECGs (electrocardiograms).
measure: Genomic Predictors of Response Rate and PFS
time frame: 30 months
description: Blood (about 1-2 tablespoons) collected for biomarker and routine tests and to evaluate the ORR and PFS.
arm group label: Intervention
arm group type: Experimental
description: All patients received clarithromycin, lenalidomide, and dexamethasone in 28-day cycles. Dexamethasone (40 mg) was given orally on days 1, 8, 15, and 22. Clarithromycin (500 mg) was given orally twice daily.Lenalidomide (25 mg) was given orally daily on days 1 to 21
intervention type: Drug
intervention name: clarithromycin
description: Clarithromycin 500mg PO twice daily on days 1-28 for a 28-day cycle.
arm group label: Intervention
other name: Biaxin
intervention type: Drug
intervention name: Lenalidomide
description: Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle
arm group label: Intervention
other name: Revlimid
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle.
arm group label: Intervention
other name: hexadecadrol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: zhongjun xia, MD.
role: Principal Investigator
affiliation: hematological oncology department
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: wanghua
investigator title: professor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Clarithromycin
mesh term: Dexamethasone
mesh term: Lenalidomide
sharing ipd: No