<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/NCT02188368</url>
  </required_header>
  <id_info>
    <org_study_id>PO-CL-MM-PI-003854</org_study_id>
    <nct_id>NCT02188368</nct_id>
  </id_info>
  <brief_title>Pomalidomide for Lenalidomide for Relapsed or Refractory Multiple Myeloma Patients</brief_title>
  <official_title>A Phase 2 Study of Pomalidomide as a Replacement for Lenalidomide for Multiple Myeloma Patients Relapsed or Refractory to a Lenalidomide-Containing Combination Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oncotherapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Oncotherapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this clinical research study is to evaluate the safety and effectiveness (good&#xD;
      and bad effects) of pomalidomide given as part of a combination therapy that include more&#xD;
      than just steroids to treat subjects with relapsed (subjects whose disease came back) or&#xD;
      refractory (subjects whose disease did not respond to past treatment) multiple myeloma (MM).&#xD;
&#xD;
      Pomalidomide (alone or in combination with dexamethasone) has been approved by the United&#xD;
      States Food and Drug Administration (FDA) for the treatment of MM patients who have received&#xD;
      at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated&#xD;
      disease progression on or within 60 days of completion of their last therapy. However, the&#xD;
      use of pomalidomide in combination with other drugs used to treat MM, such as&#xD;
      chemotherapeutic agents and proteasome inhibitors, is currently being tested and is not&#xD;
      approved. Pomalidomide is in the same drug class as thalidomide and lenalidomide. Like&#xD;
      lenalidomide, pomalidomide is a drug that alters the immune system and it may also interfere&#xD;
      with the development of small blood vessels that help support tumor growth. Therefore, in&#xD;
      theory, it may reduce or prevent the growth of cancer cells. The testing done with&#xD;
      pomalidomide thus far has shown that it is well-tolerated and effective for subjects with MM&#xD;
      both on its own and in combination with dexamethasone. Using another drug class, namely&#xD;
      proteasome inhibitors, we have demonstrated that simply replacing a proteasome inhibitor with&#xD;
      another in an established anti-myeloma treatment regimen can frequently overcome resistance&#xD;
      regardless of the other agents that are part of the anti-myeloma regimen. Importantly, the&#xD;
      toxicity profile of the new combinations closely resembled that of the proteasome inhibitor&#xD;
      administered as a single agent. Based on this experience, we hypothesize that the replacement&#xD;
      of lenalidomide with pomalidomide will yield similar results in a similar relapsed/refractory&#xD;
      MM patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 2, multicenter, open-label and non-randomized study to evaluate the efficacy&#xD;
      and safety of pomalidomide as a replacement for lenalidomide among MM patients who have&#xD;
      failed lenalidomide-containing regimens that include more than steroids within 6 months of&#xD;
      their last dose of lenalidomide. Pomalidomide will replace lenalidomide in a combination&#xD;
      regimen containing an alkylating agent (cyclophosphamide), anthracycline (doxorubicin or&#xD;
      PLD), proteasome inhibitor (bortezomib or carfilzomib) and/or a glucocorticosteroid&#xD;
      (prednisone, dexamethasone or methylprednisolone). Pomalidomide will be administered on days&#xD;
      1-21 of a 28-day cycle, whereas other drugs (anthracyclines, proteasome inhibitors, steroids&#xD;
      or alkylating agents except melphalan) will be administered using the same schedule(s),&#xD;
      dose(s) and drug combination as the last lenalidomide-containing regimen that the patient&#xD;
      received and failed. This study will enroll patients resistant to a lenalidomide-containing&#xD;
      combination regimen as demonstrated by PD while being treated or that has relapsed within 6&#xD;
      months of the last dose of lenalidomide in their last lenalidomide-containing combination&#xD;
      regimen or while on lenalidomide or lenalidomide and steroid maintenance therapy. Forty-five&#xD;
      patients will be enrolled in the study.&#xD;
&#xD;
      The study consists of: 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) a&#xD;
      final assessment to occur 28 days after the end of the last treatment cycle; and 4) a&#xD;
      follow-up period.&#xD;
&#xD;
      Subjects eligible for this study will receive treatment with study drug for a maximum of&#xD;
      eight 28-day treatment cycles, depending on the schedule of their last&#xD;
      lenalidomide-containing regimen. Subjects are to be treated to a maximum response (lowest&#xD;
      level of paraprotein) plus 1 additional cycle, without exceeding a total of 8 cycles, or&#xD;
      complete 8 cycles of therapy without progressing (PD).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>Cycles 1-3 for selected regimens (up to 3 months)</time_frame>
    <description>MTD will be determined for any ≥ three-drug combinations other than:&#xD;
bortezomib + steroids + lenalidomide; carfilzomib + steroids + lenalidomide; clarithromycin + steroids + lenalidomide; cyclophosphamide + steroids + lenalidomide pegylated liposomal doxorubicin (PLD) + lenalidomide with or without steroids</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Adverse events will be graded via the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Overall response rate (ORR): complete response (CR)+ very good partial response (VGPR) + partial response (PR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>CBR=ORR + minor response (MR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>time from initiation of therapy to progressive disease (assessed at least over 36 months)</time_frame>
    <description>The time from the initiation of therapy to progressive disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>time from initiation of therapy to progressive disease or death from any cause, whichever comes first (assessed at least over 36 months)</time_frame>
    <description>Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first response (TTP)</measure>
    <time_frame>time from initiation of therapy to the first evidence of a confirmed response (up to 36 months)</time_frame>
    <description>time from initiation of therapy to the first evidence of a confirmed response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>time from the first response (&gt; PR) to progressive disease (assessed at least over 36 months)</time_frame>
    <description>time from the first response (&gt; PR) to progressive disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>time from initiation of therapy to death from any cause or last follow-up visit (assessed at least over 36 months).</time_frame>
    <description>time from initiation of therapy to death from any cause or last follow-up visit</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>POM 4 mg PO days 1-21 Steroids at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).&#xD;
BTZ (bortezomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).&#xD;
CFZ (carfilzomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).&#xD;
CLA (clarithromycin) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).&#xD;
CY (cyclophosphamide) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: POM 3mg+PLD with or without steroids</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>POM 3 mg PO days 1-21 Steroids (if the patient had received them) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).&#xD;
PLD at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: POM MTD + other drugs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1:&#xD;
POM at escalating doses of 2 mg (Cycle 1), 3 mg (Cycle 2) or 4 mg (Cycle 3+) All other agents at the same dose and on the same days as the patients were receiving them in the lenalidomide-containing regimen they had failed&#xD;
Phase 2:&#xD;
POM at the MTD All other agents, at the same dose and on the same days as phase 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>POM</intervention_name>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <arm_group_label>B: POM 3mg+PLD with or without steroids</arm_group_label>
    <arm_group_label>C: POM MTD + other drugs</arm_group_label>
    <other_name>Pomalidomide</other_name>
    <other_name>Pomalyst</other_name>
    <other_name>Actimid</other_name>
    <other_name>CC-4047</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Steroids</intervention_name>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <arm_group_label>B: POM 3mg+PLD with or without steroids</arm_group_label>
    <other_name>Dexamethasone</other_name>
    <other_name>prednisone</other_name>
    <other_name>methyprednisolone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PLD</intervention_name>
    <arm_group_label>B: POM 3mg+PLD with or without steroids</arm_group_label>
    <other_name>Pegylated liposomal doxirrubicin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CFZ</intervention_name>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <other_name>Carfilzomib</other_name>
    <other_name>Kyprolis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BTZ</intervention_name>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <other_name>Bortezomib</other_name>
    <other_name>Velcade</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CLA</intervention_name>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <other_name>Clarithromycin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CY</intervention_name>
    <arm_group_label>A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)</arm_group_label>
    <other_name>Cyclophosphamide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Has a diagnosis of MM based on standard criteria as follows:&#xD;
&#xD;
               -  Major criteria:&#xD;
&#xD;
                    1. plasmacytomas on tissue biopsy&#xD;
&#xD;
                    2. bone marrow plasmacytosis (greater than 30% plasma cells)&#xD;
&#xD;
                    3. monoclonal immunoglobulin (Ig) spike on serum electrophoresis IgG greater&#xD;
                       than 3.5 g/dL or IgA greater than 2.0 g/dL; kappa or lambda light chain&#xD;
                       excretion greater than 1 g/day on 24-hour urine protein electrophoresis&#xD;
&#xD;
               -  Minor criteria:&#xD;
&#xD;
                    1. bone marrow plasmacytosis (10% to 30% plasma cells)&#xD;
&#xD;
                    2. monoclonal immunoglobulin present but of lesser magnitude than given under&#xD;
                       major criteria&#xD;
&#xD;
                    3. lytic bone lesions&#xD;
&#xD;
                    4. normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600&#xD;
                       mg/dL&#xD;
&#xD;
               -  Any of the following sets of criteria will confirm the diagnosis of multiple&#xD;
                  myeloma:&#xD;
&#xD;
                    -  any 2 of the major criteria&#xD;
&#xD;
                    -  major criterion 1 plus minor criterion 2, 3, or 4&#xD;
&#xD;
                    -  major criterion 3 plus minor criterion 1 or 3&#xD;
&#xD;
                    -  minor criteria 1, 2, and 3, or 1, 2, and 4&#xD;
&#xD;
          2. Currently has progressive MM that has relapsed while currently receiving or within 6&#xD;
             months of receiving the maximum tolerated dose of lenalidomide at the physician's&#xD;
             discretion as part of a combination treatment that includes more than just steroids in&#xD;
             a 21-day or a 28-day cycle schedule. MM patients that are relapsed or have refractory&#xD;
             disease, as defined below, are both eligible for enrollment provided they fulfill the&#xD;
             other eligibility criteria:&#xD;
&#xD;
               -  Patients are refractory to a lenalidomide combination regimen, when they progress&#xD;
                  while currently receiving the lenalidomide combination treatment or within 8&#xD;
                  weeks of its last dose.&#xD;
&#xD;
               -  Patients are considered relapsed, when they progress between 8 and 26- weeks from&#xD;
                  their last dose of lenalidomide as part of a lenalidomide-combination therapy&#xD;
                  that includes more than just steroids.&#xD;
&#xD;
               -  Prior treatment with four days or less of a total of 400 mg of prednisone (or an&#xD;
                  equivalent potency of another steroid) for MM will not be considered a regimen&#xD;
&#xD;
          3. Currently has MM with measurable disease, defined as:&#xD;
&#xD;
               -  a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL&#xD;
                  and/or&#xD;
&#xD;
               -  urine monoclonal protein levels of at least 200 mg/24 hours&#xD;
&#xD;
               -  for patients without measurable serum and urine M-protein levels, an abnormal&#xD;
                  free light chain ratio (normal value: 0.26 - 1.65)&#xD;
&#xD;
               -  Serum free light chain (SFLC) &gt; 100 mg/L (involved light chain) and abnormal ƙ/λ&#xD;
                  ratio&#xD;
&#xD;
          4. Patients with previous clotting or thrombotic events must be able to take aspirin&#xD;
             (acetylsalicylic acid, ASA) at 81 or 325 mg /daily as prophylactic anticoagulation&#xD;
             (subjects intolerant to ASA may use warfarin or low molecular weight heparin) and/or&#xD;
             antithrombotic agents.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal&#xD;
             protein (M-protein) and skin changes (POEMS) syndrome&#xD;
&#xD;
          2. Plasma cell leukemia&#xD;
&#xD;
          3. Primary amyloidosis&#xD;
&#xD;
          4. Non-hematologic malignancy within the past 5 years with the exception of a) adequately&#xD;
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)&#xD;
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or&#xD;
             less with stable prostate-specific antigen levels; or d) cancer considered cured by&#xD;
             surgical resection or unlikely to impact survival during the duration of the study,&#xD;
             such as localized transitional cell carcinoma of the bladder or benign tumors of the&#xD;
             adrenal or pancreas&#xD;
&#xD;
          5. Impaired cardiac function or clinically significant cardiac diseases, including&#xD;
             myocardial infarction within 6 months prior to enrollment, New York Heart Association&#xD;
             (NYHA) Class II or greater heart failure, uncontrolled angina, clinically significant&#xD;
             pericardial disease, severe uncontrolled ventricular arrhythmias, echocardiogram or&#xD;
             multigated acquisition scan (MUGA) evidence of left ventricular ejection fraction&#xD;
             (LVEF) below institutional normal within 28 days prior to enrollment,&#xD;
             electrocardiographic evidence of acute ischemia or active conduction system&#xD;
             abnormalities. Prior to study entry, any ECG abnormality at Screening has to be&#xD;
             documented by the investigator as not medically relevant.&#xD;
&#xD;
          6. Received the following prior therapy:&#xD;
&#xD;
               -  Pomalidomide&#xD;
&#xD;
               -  Lenalidomide alone or in combination with steroids in their last treatment&#xD;
                  regimen. Interim therapy not containing lenalidomide between their last&#xD;
                  lenalidomide-containing regimen and the start of the trial.&#xD;
&#xD;
               -  A melphalan-containing regimen as the immediate prior line of treatment&#xD;
&#xD;
               -  Chemotherapy within 3 weeks of study drugs (6 weeks for nitrosoureas)&#xD;
&#xD;
               -  Corticosteroids (&gt;10 mg /daily prednisone or equivalent) within 3 weeks of study&#xD;
                  drugs&#xD;
&#xD;
               -  Immunotherapy or antibody therapy as well as thalidomide, lenalidomide, arsenic&#xD;
                  trioxide or bortezomib within 21 days before study drugs&#xD;
&#xD;
               -  Extensive radiation therapy within 28 days before study drugs. Receipt of&#xD;
                  localized radiation therapy does not preclude enrollment.&#xD;
&#xD;
               -  Use of any other experimental drug or therapy within 28 days of study drugs&#xD;
&#xD;
          7. Known hypersensitivity to compounds of similar chemical or biological composition to&#xD;
             thalidomide and lenalidomide.&#xD;
&#xD;
          8. The development of erythema nodosum if characterized by a desquamating rash while&#xD;
             taking thalidomide or similar drugs&#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>James R Berenson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>James R. Berenson MD, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>California Cancer Associates for Research &amp; Excellence (cCARE)</name>
      <address>
        <city>Encinitas</city>
        <state>California</state>
        <zip>92024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Care Research Group</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Center at Desert Regional Medical Center</name>
      <address>
        <city>Palm Springs</city>
        <state>California</state>
        <zip>92262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inland Hematology Oncology Medical Group, Inc</name>
      <address>
        <city>San Bernardino</city>
        <state>California</state>
        <zip>92404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellness Oncology and Hematology</name>
      <address>
        <city>West Hills</city>
        <state>California</state>
        <zip>91307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James R. Berenson, MD, Inc.</name>
      <address>
        <city>West Hollywood</city>
        <state>California</state>
        <zip>90069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Sierra Nevada</name>
      <address>
        <city>Reno</city>
        <state>Nevada</state>
        <zip>89502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Juan Oncology Associates</name>
      <address>
        <city>Farmington</city>
        <state>New Mexico</state>
        <zip>87401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rapid City Regional Hospital</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellmont Medical Associates Oncology and Hematology</name>
      <address>
        <city>Kingsport</city>
        <state>Tennessee</state>
        <zip>37660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vista Oncology</name>
      <address>
        <city>Olympia</city>
        <state>Washington</state>
        <zip>98502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>August 12, 2020</last_update_submitted>
  <last_update_submitted_qc>August 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pomalidomide</keyword>
  <keyword>Lenalidomide refractory</keyword>
  <keyword>multiple myeloma</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>Clarithromycin</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Pomalidomide</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/NCT02188368
org study id: PO-CL-MM-PI-003854
nct id: NCT02188368
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this clinical research study is to evaluate the safety and effectiveness (good
      and bad effects) of pomalidomide given as part of a combination therapy that include more
      than just steroids to treat subjects with relapsed (subjects whose disease came back) or
      refractory (subjects whose disease did not respond to past treatment) multiple myeloma (MM).

      Pomalidomide (alone or in combination with dexamethasone) has been approved by the United
      States Food and Drug Administration (FDA) for the treatment of MM patients who have received
      at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated
      disease progression on or within 60 days of completion of their last therapy. However, the
      use of pomalidomide in combination with other drugs used to treat MM, such as
      chemotherapeutic agents and proteasome inhibitors, is currently being tested and is not
      approved. Pomalidomide is in the same drug class as thalidomide and lenalidomide. Like
      lenalidomide, pomalidomide is a drug that alters the immune system and it may also interfere
      with the development of small blood vessels that help support tumor growth. Therefore, in
      theory, it may reduce or prevent the growth of cancer cells. The testing done with
      pomalidomide thus far has shown that it is well-tolerated and effective for subjects with MM
      both on its own and in combination with dexamethasone. Using another drug class, namely
      proteasome inhibitors, we have demonstrated that simply replacing a proteasome inhibitor with
      another in an established anti-myeloma treatment regimen can frequently overcome resistance
      regardless of the other agents that are part of the anti-myeloma regimen. Importantly, the
      toxicity profile of the new combinations closely resembled that of the proteasome inhibitor
      administered as a single agent. Based on this experience, we hypothesize that the replacement
      of lenalidomide with pomalidomide will yield similar results in a similar relapsed/refractory
      MM patient population.
This is a phase 2, multicenter, open-label and non-randomized study to evaluate the efficacy
      and safety of pomalidomide as a replacement for lenalidomide among MM patients who have
      failed lenalidomide-containing regimens that include more than steroids within 6 months of
      their last dose of lenalidomide. Pomalidomide will replace lenalidomide in a combination
      regimen containing an alkylating agent (cyclophosphamide), anthracycline (doxorubicin or
      PLD), proteasome inhibitor (bortezomib or carfilzomib) and/or a glucocorticosteroid
      (prednisone, dexamethasone or methylprednisolone). Pomalidomide will be administered on days
      1-21 of a 28-day cycle, whereas other drugs (anthracyclines, proteasome inhibitors, steroids
      or alkylating agents except melphalan) will be administered using the same schedule(s),
      dose(s) and drug combination as the last lenalidomide-containing regimen that the patient
      received and failed. This study will enroll patients resistant to a lenalidomide-containing
      combination regimen as demonstrated by PD while being treated or that has relapsed within 6
      months of the last dose of lenalidomide in their last lenalidomide-containing combination
      regimen or while on lenalidomide or lenalidomide and steroid maintenance therapy. Forty-five
      patients will be enrolled in the study.

      The study consists of: 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) a
      final assessment to occur 28 days after the end of the last treatment cycle; and 4) a
      follow-up period.

      Subjects eligible for this study will receive treatment with study drug for a maximum of
      eight 28-day treatment cycles, depending on the schedule of their last
      lenalidomide-containing regimen. Subjects are to be treated to a maximum response (lowest
      level of paraprotein) plus 1 additional cycle, without exceeding a total of 8 cycles, or
      complete 8 cycles of therapy without progressing (PD).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: Cycles 1-3 for selected regimens (up to 3 months)
description: MTD will be determined for any ≥ three-drug combinations other than:
bortezomib + steroids + lenalidomide; carfilzomib + steroids + lenalidomide; clarithromycin + steroids + lenalidomide; cyclophosphamide + steroids + lenalidomide pegylated liposomal doxorubicin (PLD) + lenalidomide with or without steroids
measure: Number of subjects with adverse events
time frame: up to 36 months
description: Adverse events will be graded via the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.
measure: Overall Response Rate
time frame: up to 36 months
description: Overall response rate (ORR): complete response (CR)+ very good partial response (VGPR) + partial response (PR)
measure: Clinical Benefit Rate (CBR)
time frame: up to 36 months
description: CBR=ORR + minor response (MR)
measure: Time to Progression
time frame: time from initiation of therapy to progressive disease (assessed at least over 36 months)
description: The time from the initiation of therapy to progressive disease
measure: Progression-free survival (PFS)
time frame: time from initiation of therapy to progressive disease or death from any cause, whichever comes first (assessed at least over 36 months)
description: Time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
measure: Time to first response (TTP)
time frame: time from initiation of therapy to the first evidence of a confirmed response (up to 36 months)
description: time from initiation of therapy to the first evidence of a confirmed response
measure: Duration of response (DOR)
time frame: time from the first response (> PR) to progressive disease (assessed at least over 36 months)
description: time from the first response (> PR) to progressive disease
measure: Overall survival (OS)
time frame: time from initiation of therapy to death from any cause or last follow-up visit (assessed at least over 36 months).
description: time from initiation of therapy to death from any cause or last follow-up visit
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
arm group type: Experimental
description: POM 4 mg PO days 1-21 Steroids at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
BTZ (bortezomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
CFZ (carfilzomib) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
CLA (clarithromycin) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
CY (cyclophosphamide) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
arm group label: B: POM 3mg+PLD with or without steroids
arm group type: Experimental
description: POM 3 mg PO days 1-21 Steroids (if the patient had received them) at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
PLD at the same dose and on the same days as the patient's lenalidomide-containing treatment (it varies for each subject).
arm group label: C: POM MTD + other drugs
arm group type: Experimental
description: Phase 1:
POM at escalating doses of 2 mg (Cycle 1), 3 mg (Cycle 2) or 4 mg (Cycle 3+) All other agents at the same dose and on the same days as the patients were receiving them in the lenalidomide-containing regimen they had failed
Phase 2:
POM at the MTD All other agents, at the same dose and on the same days as phase 1
intervention type: Drug
intervention name: POM
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
arm group label: B: POM 3mg+PLD with or without steroids
arm group label: C: POM MTD + other drugs
other name: Pomalidomide
other name: Pomalyst
other name: Actimid
other name: CC-4047
intervention type: Drug
intervention name: Steroids
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
arm group label: B: POM 3mg+PLD with or without steroids
other name: Dexamethasone
other name: prednisone
other name: methyprednisolone
intervention type: Drug
intervention name: PLD
arm group label: B: POM 3mg+PLD with or without steroids
other name: Pegylated liposomal doxirrubicin
intervention type: Drug
intervention name: CFZ
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
other name: Carfilzomib
other name: Kyprolis
intervention type: Drug
intervention name: BTZ
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
other name: Bortezomib
other name: Velcade
intervention type: Drug
intervention name: CLA
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
other name: Clarithromycin
intervention type: Drug
intervention name: CY
arm group label: A: POM 4mg+Steroids+(CFZ, BTZ, CY or CLA)
other name: Cyclophosphamide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James R Berenson, MD
role: Principal Investigator
affiliation: James R. Berenson MD, Inc.
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country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Clarithromycin
mesh term: Dexamethasone
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Bortezomib
mesh term: Pomalidomide