<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/NCT04405167</url>
  </required_header>
  <id_info>
    <org_study_id>842603, UPCC 45419</org_study_id>
    <secondary_id>UPCC 45419</secondary_id>
    <nct_id>NCT04405167</nct_id>
  </id_info>
  <brief_title>Tasquinimod for the Treatment of Relapsed or Refractory Myeloma</brief_title>
  <official_title>Phase 1 Study of Tasquinimod Alone and in Combination With Standard Therapy for Relapsed or Refractory Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Active Biotech AB</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</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 study is the first study of tasquinimod, an inhibitor of S100A9, in patients with&#xD;
      multiple myeloma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tasquinimod has previously been studied as an anti-cancer agent in patients with other&#xD;
      cancers, including a phase 3 randomized trial in patients with metastatic prostate cancer&#xD;
      that showed an improvement in radiographic progression-free survival. The side effect profile&#xD;
      of tasquinimod is well-characterized based on this previous experience. This trial will&#xD;
      establish a maximum tolerated dose and optimal schedule for administration of tasquinimod in&#xD;
      patients with multiple myeloma and then investigate the maximum tolerated dose of tasquinimod&#xD;
      in combination with a standard myeloma regimen of ixazomib, lenalidomide, and dexamethasone&#xD;
      (IRd). For both single agent tasquinimod and the combination of tasquinimod with IRd,&#xD;
      exploratory expansion cohorts will be enrolled to preliminarily characterize the antimyeloma&#xD;
      activity of each regimen.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 10, 2020</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Open label phase 1 study with pilot expansion cohorts at the maximum tolerated dose</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Optimal Dose</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Maximum tolerated dose of single agent tasquinimod (mg).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preliminary Single-Agent Toxicity Profile</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Percentage of subjects experiencing treatment-emergent grade 3/4 adverse events during therapy with single-agent tasquinimod (using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary Combination Therapy Toxicity Profile</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Percentage of subjects experiencing treatment-emergent grade 3/4 adverse events during therapy with tasquinimod, ixazomib, lenalidomide, and dexamethasone (using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary Single-Agent Response</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Percentage of subjects achieving a partial response or better with single-agent tasquinimod (using the response criteria of the International Myeloma Working Group)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary Assessment of Clinical Response Combination Therapy</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Percentage of subjects achieving a partial response or better with tasquinimod, ixazomib, lenalidomide, and dexamethasone (using the response criteria of the International Myeloma Working Group)</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">34</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>A1: Tasquinimod single agent dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>There are up to 5 planned dose levels, with 3 de-escalation dose levels available in case dose level 1 is determined to exceed the MTD. This arm will enroll 15-30 subjects if all dose levels are explored.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A2: Tasquinimod single agent expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Additional subjects will enroll in arm A2 at the MTD and optimal schedule, so that 12 subjects total who are evaluable for response will have received the MTD/optimal schedule of single agent tasquinimod. Enrollment in arm A2 will not begin until enrollment in arm A1 has been completed and a single agent MTD/optimal schedule has been established.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B1: Tasquinimod+IRd dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose levels will be defined according to the same tasquinimod doses as in the single agent (Arm A1) dose escalation. Enrollment in arm B1 will not begin until enrollment in arm A1 has been completed and an MTD/optimal schedule has been established for single agent tasquinimod. Initial subjects in arm B1 will be enrolled at the lower of dose level 1 or one dose level below the single agent MTD . If this initial dose level is determined to exceed the combination MTD, further subjects will be enrolled at one dose level lower. Enrollment is not planned in arm B1 at doses higher than the single agent MTD. There are 9-12 planned subjects if all dose levels are explored.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B2: Tasquinimod+IRd expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Additional subjects will enroll in arm B2 at the MTD and optimal schedule, so that 12 subjects total who are both evaluable for response and previously refractory to their most recent Imid/PI combination will have received the MTD/optimal schedule of tasquinimod in combination with ixazomib, lenalidomide, and dexamethasone. Enrollment in arm B2 will not begin until enrollment in arm B1 has been completed and a combination MTD/optimal schedule has been established.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tasquinimod</intervention_name>
    <description>Tasquinimod will be supplied as oral capsules.</description>
    <arm_group_label>A1: Tasquinimod single agent dose escalation</arm_group_label>
    <arm_group_label>A2: Tasquinimod single agent expansion</arm_group_label>
    <arm_group_label>B1: Tasquinimod+IRd dose escalation</arm_group_label>
    <arm_group_label>B2: Tasquinimod+IRd expansion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IRd chemotherapy</intervention_name>
    <description>IRd chemotherapy with ixazomib, lenalidomide, and dexamethasone</description>
    <arm_group_label>B1: Tasquinimod+IRd dose escalation</arm_group_label>
    <arm_group_label>B2: Tasquinimod+IRd expansion</arm_group_label>
    <other_name>Ixazomib, Lenalidomide, Dexamethasone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. 18 years of age or older&#xD;
&#xD;
          3. Multiple myeloma (MM) diagnosed according to IMWG criteria&#xD;
&#xD;
          4. Measurable disease (this is defined differently in different arms)&#xD;
&#xD;
          5. Multiple myeloma relapsed or refractory to treatment (this is defined differently in&#xD;
             different arms)&#xD;
&#xD;
          6. Meet certain clinical laboratory criteria&#xD;
&#xD;
          7. ECOG performance status ≤2&#xD;
&#xD;
          8. Life expectancy of at least 3 months&#xD;
&#xD;
          9. For women of childbearing potential, a negative serum or urine pregnancy test prior to&#xD;
             study treatment.&#xD;
&#xD;
         10. For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile&#xD;
             (absence of ovaries and/or uterus): agreement to use two methods of contraception one&#xD;
             of which must be highly effective&#xD;
&#xD;
         11. For men: agreement to use a barrier method of contraception for 1 month before start&#xD;
             of study treatment, during the treatment period and for 6 months after the last dose&#xD;
             of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Failure to have fully recovered (i.e. ≤ Grade 1 toxicity) from the effects of prior&#xD;
             chemotherapy (except for alopecia)&#xD;
&#xD;
          2. Active graft versus host disease&#xD;
&#xD;
          3. Treatment with any of the following:&#xD;
&#xD;
               1. Cytotoxic chemotherapy within 3 weeks prior to the initiation of study treatment&#xD;
&#xD;
               2. Proteasome inhibitors, Imids, or monoclonal antibodies within 2 weeks prior to&#xD;
                  the initiation of study treatment&#xD;
&#xD;
               3. Experimental therapy within 4 weeks or 5 half-lives, whichever is shorter&#xD;
&#xD;
               4. Systemic corticosteroids &gt;=10 mg prednisone or equivalent within 7 days prior to&#xD;
                  the initiation of study treatment&#xD;
&#xD;
               5. Radiotherapy within 7 days prior to initiating study treatment&#xD;
&#xD;
               6. Plasmapheresis within 4 weeks prior to the initiation of study treatment&#xD;
&#xD;
               7. Tasquinimod at any time&#xD;
&#xD;
          4. Known central nervous system involvement by myeloma&#xD;
&#xD;
          5. Diagnosis of smoldering multiple myeloma&#xD;
&#xD;
          6. Diagnosis of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal protein, and skin changes)&#xD;
&#xD;
          7. Active plasma cell leukemia&#xD;
&#xD;
          8. Symptomatic primary (AL) amyloidosis&#xD;
&#xD;
          9. Diagnosis of myelodysplastic syndrome or myeloproliferative syndrome&#xD;
&#xD;
         10. Active other malignancy&#xD;
&#xD;
         11. Major surgery within 4 weeks prior to initiating study treatment&#xD;
&#xD;
         12. Evidence of severe or currently uncontrolled cardiovascular condition&#xD;
&#xD;
         13. Ongoing or active systemic infection that requires systemic antibiotic or parenteral&#xD;
             anti-infective therapy&#xD;
&#xD;
         14. Active tuberculosis, active hepatitis A, B or C virus infection, or known human&#xD;
             immunodeficiency virus (HIV) positive&#xD;
&#xD;
         15. History of pancreatitis&#xD;
&#xD;
         16. History of malabsorption or other condition that would interfere with absorption of&#xD;
             study drugs&#xD;
&#xD;
         17. Systemic treatment within 14 days prior to the initiation of study treatment with&#xD;
             moderate or strong inhibitor or moderate or strong inducer of cytochrome P-3A4&#xD;
             (CYP3A4)&#xD;
&#xD;
         18. Need for ongoing therapy drug substances of narrow therapeutic range that are&#xD;
             metabolized mainly by CYP3A4 (alfentanil, fentanyl, quinidine, astemizole,&#xD;
             terfenadine, sirolimus, tacrolimus, cyclosporine, cisapride, ergotamine)&#xD;
&#xD;
         19. Need for ongoing therapy with drug substances of narrow therapeutic range metabolized&#xD;
             mainly by CYP1A2 (duloxetine, alosetron, theophylline, tizanidine, ondansetron)&#xD;
&#xD;
         20. Ongoing treatment with warfarin, unless the INR is &lt;=3.0.&#xD;
&#xD;
         21. For subjects enrolled on the IRd combination arms, prior dose-limiting toxicity with&#xD;
             lenalidomide or ixazomib or absolute contraindication to concomitant thrombosis&#xD;
             prophylaxis&#xD;
&#xD;
         22. Peripheral neuropathy grade ≥2 (NCI-CTCAE)&#xD;
&#xD;
         23. Known hypersensitivity to tasquinimod or any excipients in the study treatments&#xD;
&#xD;
         24. Pregnant or nursing (lactating) women&#xD;
&#xD;
         25. Any other condition that would, in the Investigator's judgment, contraindicate&#xD;
             subject's participation in the clinical study due to safety concerns or compliance&#xD;
             with clinical study procedures&#xD;
&#xD;
         26. Prior inclusion in this study&#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>Dan Vogl, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dan Vogl, MD</last_name>
    <phone>215-662-7140</phone>
    <email>dan.vogl@pennmedicine.upenn.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dan Vogl, MD</last_name>
      <phone>215-662-7140</phone>
      <email>dan.vogl@pennmedicine.upenn.edu</email>
    </contact>
    <investigator>
      <last_name>Dan Vogl, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>March 11, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</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 14, 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>Dexamethasone</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Ixazomib</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/NCT04405167
org study id: 842603, UPCC 45419
secondary id: UPCC 45419
nct id: NCT04405167
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is the first study of tasquinimod, an inhibitor of S100A9, in patients with
      multiple myeloma.
Tasquinimod has previously been studied as an anti-cancer agent in patients with other
      cancers, including a phase 3 randomized trial in patients with metastatic prostate cancer
      that showed an improvement in radiographic progression-free survival. The side effect profile
      of tasquinimod is well-characterized based on this previous experience. This trial will
      establish a maximum tolerated dose and optimal schedule for administration of tasquinimod in
      patients with multiple myeloma and then investigate the maximum tolerated dose of tasquinimod
      in combination with a standard myeloma regimen of ixazomib, lenalidomide, and dexamethasone
      (IRd). For both single agent tasquinimod and the combination of tasquinimod with IRd,
      exploratory expansion cohorts will be enrolled to preliminarily characterize the antimyeloma
      activity of each regimen.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Open label phase 1 study with pilot expansion cohorts at the maximum tolerated dose
primary purpose: Treatment
masking: None (Open Label)
measure: Optimal Dose
time frame: approximately 3 years
description: Maximum tolerated dose of single agent tasquinimod (mg).
measure: Preliminary Single-Agent Toxicity Profile
time frame: approximately 3 years
description: Percentage of subjects experiencing treatment-emergent grade 3/4 adverse events during therapy with single-agent tasquinimod (using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5)
measure: Preliminary Combination Therapy Toxicity Profile
time frame: approximately 3 years
description: Percentage of subjects experiencing treatment-emergent grade 3/4 adverse events during therapy with tasquinimod, ixazomib, lenalidomide, and dexamethasone (using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5)
measure: Preliminary Single-Agent Response
time frame: approximately 3 years
description: Percentage of subjects achieving a partial response or better with single-agent tasquinimod (using the response criteria of the International Myeloma Working Group)
measure: Preliminary Assessment of Clinical Response Combination Therapy
time frame: approximately 3 years
description: Percentage of subjects achieving a partial response or better with tasquinimod, ixazomib, lenalidomide, and dexamethasone (using the response criteria of the International Myeloma Working Group)
arm group label: A1: Tasquinimod single agent dose escalation
arm group type: Experimental
description: There are up to 5 planned dose levels, with 3 de-escalation dose levels available in case dose level 1 is determined to exceed the MTD. This arm will enroll 15-30 subjects if all dose levels are explored.
arm group label: A2: Tasquinimod single agent expansion
arm group type: Experimental
description: Additional subjects will enroll in arm A2 at the MTD and optimal schedule, so that 12 subjects total who are evaluable for response will have received the MTD/optimal schedule of single agent tasquinimod. Enrollment in arm A2 will not begin until enrollment in arm A1 has been completed and a single agent MTD/optimal schedule has been established.
arm group label: B1: Tasquinimod+IRd dose escalation
arm group type: Experimental
description: Dose levels will be defined according to the same tasquinimod doses as in the single agent (Arm A1) dose escalation. Enrollment in arm B1 will not begin until enrollment in arm A1 has been completed and an MTD/optimal schedule has been established for single agent tasquinimod. Initial subjects in arm B1 will be enrolled at the lower of dose level 1 or one dose level below the single agent MTD . If this initial dose level is determined to exceed the combination MTD, further subjects will be enrolled at one dose level lower. Enrollment is not planned in arm B1 at doses higher than the single agent MTD. There are 9-12 planned subjects if all dose levels are explored.
arm group label: B2: Tasquinimod+IRd expansion
arm group type: Experimental
description: Additional subjects will enroll in arm B2 at the MTD and optimal schedule, so that 12 subjects total who are both evaluable for response and previously refractory to their most recent Imid/PI combination will have received the MTD/optimal schedule of tasquinimod in combination with ixazomib, lenalidomide, and dexamethasone. Enrollment in arm B2 will not begin until enrollment in arm B1 has been completed and a combination MTD/optimal schedule has been established.
intervention type: Drug
intervention name: Tasquinimod
description: Tasquinimod will be supplied as oral capsules.
arm group label: A1: Tasquinimod single agent dose escalation
arm group label: A2: Tasquinimod single agent expansion
arm group label: B1: Tasquinimod+IRd dose escalation
arm group label: B2: Tasquinimod+IRd expansion
intervention type: Drug
intervention name: IRd chemotherapy
description: IRd chemotherapy with ixazomib, lenalidomide, and dexamethasone
arm group label: B1: Tasquinimod+IRd dose escalation
arm group label: B2: Tasquinimod+IRd expansion
other name: Ixazomib, Lenalidomide, Dexamethasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dan Vogl, MD
role: Principal Investigator
affiliation: University of Pennsylvania
last name: Dan Vogl, MD
phone: 215-662-7140
email: dan.vogl@pennmedicine.upenn.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
mesh term: Lenalidomide
mesh term: Ixazomib
sharing ipd: No