xml: <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/NCT05994235</url>
    </required_header>
    <id_info>
      <org_study_id>23-06026184</org_study_id>
      <secondary_id>22-10025285</secondary_id>
      <nct_id>NCT05994235</nct_id>
    </id_info>
    <brief_title>Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma</brief_title>
    <official_title>A Phase II Trial of Tazemetostat Plus Mosunetuzumab in Untreated Follicular Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Weill Medical College of Cornell University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Epizyme, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Genentech, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Weill Medical College of Cornell University</source>
    <oversight_info>
      <has_dmc>Yes</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>
        The goal of this study is to learn about the safety and effectiveness of the combination of&#xD;
        tazemetostat pills in combination with mosunetuzumab injections for people with follicular&#xD;
        lymphoma who haven't received treatment before. The investigators hypothesize that&#xD;
        tazemetostat with mosunetuzumab has the potential to increase the efficacy of the product&#xD;
        without compromising the safety.&#xD;
  &#xD;
        Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell&#xD;
        lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and&#xD;
        enhance the immune system's ability to fight it. Tazemetostat is FDA-approved in previously&#xD;
        treated follicular lymphoma and currently undergoing study in other lymphomas.&#xD;
  &#xD;
        Mosunetuzumab is a bispecific antibody therapy that is a therapeutic strategy that uses the&#xD;
        immune system to fight lymphoma, called immunotherapy. Bispecific antibodies have two ends:&#xD;
        one attaches to T cells in the immune system and the other attaches to lymphoma cells,&#xD;
        helping guide our immune system to attack the cancer. Mosunetuzumab has been studied in&#xD;
        follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is&#xD;
        approved by the FDA to be given intravenously (directly into a vein) but is not yet approved&#xD;
        by the FDA is not yet approved as an injection under the skin, which is how it is given in&#xD;
        this study. They have not yet been studied in combination.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a phase II, open-label study. Fifty patients with previously untreated follicular&#xD;
        lymphoma will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and&#xD;
        with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning&#xD;
        at the same time as mosunetuzumab initiation. Mosunetuzumab and tazemetostat will be given in&#xD;
        28-day cycles for up to 12 cycles. Response assessments by PET/CT will occur at 12 weeks&#xD;
        post-mosunetuzumab and again at 30 and 48 weeks for those with an ongoing response to&#xD;
        treatment. Treatment with steroids, tocilizumab, growth factors, tumor lysis prophylaxis, and&#xD;
        antibiotics may be used as per standard of care at our institution. Dose modifications are&#xD;
        permitted for toxicity. There will be a follow-up visit after 2 years from starting the&#xD;
        study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2033</completion_date>
    <primary_completion_date type="Anticipated">September 2033</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>Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria</measure>
      <time_frame>Estimated day 336</time_frame>
      <description>The proportion of patients who achieve complete response as per the Lugano criteria will be calculated and their 90% confidences will be computed with Clopper-Pearson method via exact binomial distribution.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of participants who experience cytokine release syndrome (CRS)</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>CRS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants who experience Immune effector cell-associated neurotoxicity syndrome (ICANS)</measure>
      <time_frame>Day 0 to Day 28</time_frame>
      <description>ICANS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Progression-Free Survival (PFS)</measure>
      <time_frame>For a maximum of approximately 10 years</time_frame>
      <description>PFS is defined as the duration of time from start of treatment to time of progression or death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Overall Survival (OS)</measure>
      <time_frame>For a maximum of approximately 10 years</time_frame>
      <description>OS is defined as the duration of time from start of treatment to death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR) at the time of therapy completion, as defined by Lugano Criteria</measure>
      <time_frame>Estimated to be day 336</time_frame>
      <description>ORR is defined as the proportion of patients who have a partial or complete response to therapy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants who achieve a Complete Response (CR) per Lugano's Criteria</measure>
      <time_frame>For a maximum of approximately 10 years</time_frame>
      <description>Response and progression are evaluated according to the Lugano criteria for lymphoma response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Median Duration of Response</measure>
      <time_frame>For a maximum of approximately 10 years</time_frame>
      <description>The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease or death due to any cause, whichever occurs first is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Follicular Lymphoma</condition>
    <arm_group>
      <arm_group_label>Subcutaneous Mosunetuzumab and Oral Tazemetostat</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>50 patients will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mosunetuzumab</intervention_name>
      <description>Mosunetuzumab will be administered in weekly dose increments (&quot;step-up dosing&quot;) during Cycle 1 and then on Day 1 of each cycle. Mosunetuzumab will be given in 28-day cycles for up to 12 cycles. Mosunetuzumab will be administered SC at the dose of 5 mg on Day 1, 45 mg on Day 8, and 45 mg on Day 15 in Cycle 1. Beginning with Cycle 2, it will be administered SC at the dose of 45 mg on Day 1. Each cycle lasts 4 weeks.</description>
      <arm_group_label>Subcutaneous Mosunetuzumab and Oral Tazemetostat</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tazemetostat Pill</intervention_name>
      <description>Oral tazemetostat will be administered by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation until disease progression, unacceptable toxicity, or consent is withdrawn. Patients will remain on tazemetostat for up to twelve 28-day cycles from initiation of mosunetuzumab.</description>
      <arm_group_label>Subcutaneous Mosunetuzumab and Oral Tazemetostat</arm_group_label>
      <other_name>Tazverik</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Ability to comply with the study protocol&#xD;
  &#xD;
            -  Willing to use highly effective contraception, if of childbearing potential&#xD;
  &#xD;
            -  Diagnosed with follicular lymphoma (FL; Grades 1-3a)&#xD;
  &#xD;
            -  Received no prior systemic lymphoma therapy (local radiotherapy is not considered&#xD;
               systemic therapy)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inability to take oral medication OR have malabsorption syndrome or any other&#xD;
               uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might&#xD;
               impair the bioavailability of tazemetostat&#xD;
  &#xD;
            -  Grade 3b FL&#xD;
  &#xD;
            -  History of transformation of indolent disease to diffuse large B cell lymphoma&#xD;
  &#xD;
            -  Any prior history of myeloid malignancies, including myelodysplastic syndrome&#xD;
               (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN)&#xD;
  &#xD;
            -  Any prior history of T cell lymphoblastic lymphoma (T-LBL)/ T cell lymphoblastic&#xD;
               leukemia (T-ALL)&#xD;
  &#xD;
            -  Active or history of central nervous system lymphoma or leptomeningeal infiltration&#xD;
  &#xD;
            -  Prior standard or investigational systemic anti cancer therapy for lymphoma. Patients&#xD;
               who have received prior XRT will not be excluded&#xD;
  &#xD;
            -  History of solid organ transplantation&#xD;
  &#xD;
            -  History of severe allergic or anaphylactic reaction to humanized, chimeric or murine&#xD;
               monoclonal antibodies (MAbs)&#xD;
  &#xD;
            -  Known or suspected chronic active Epstein-Barr virus (EBV) infection&#xD;
  &#xD;
            -  Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)&#xD;
  &#xD;
            -  Clinically significant history of liver disease, including viral or other hepatitis,&#xD;
               or cirrhosis&#xD;
  &#xD;
            -  Active Hepatitis B or Hepatitis C infection&#xD;
  &#xD;
            -  HIV positive with CD4 count &lt;200 and not currently taking antiretroviral therapy&#xD;
  &#xD;
            -  History of progressive multifocal leukoencephalopathy (PML)&#xD;
  &#xD;
            -  Active autoimmune disease requiring treatment&#xD;
  &#xD;
            -  History of autoimmune disease, including, but not limited to: myocarditis,&#xD;
               pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus&#xD;
               erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis&#xD;
               associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's&#xD;
               syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or&#xD;
               glomerulonephritis&#xD;
  &#xD;
            -  Prior allogeneic stem cell transplant (SCT)&#xD;
  &#xD;
            -  Significant cardiovascular disease (e.g., New York Heart Association Class III or IV&#xD;
               cardiac disease, myocardial infarction within the previous 6 months, unstable&#xD;
               arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive&#xD;
               pulmonary disease or history of bronchospasm)&#xD;
  &#xD;
            -  Major surgery other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1&#xD;
               or anticipation of a major surgical procedure during the course of the study&#xD;
  &#xD;
            -  Active central nervous system disease or underlying neurologic disease such as stroke&#xD;
               or intracranial hemorrhage within 3 months prior to enrollment, history of seizure&#xD;
               disorder, or history of neurogenerative disease&#xD;
  &#xD;
            -  History of pneumonitis or interstitial lung disease&#xD;
  &#xD;
            -  Pregnant or breastfeeding or intending to become pregnant during the 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>Samuel Yamshon, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Weill Medical College of Cornell University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tejasvi Kaur Sahni</last_name>
      <phone>646-962-9337</phone>
      <email>tks4001@med.cornell.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Brittany Hobbie</last_name>
      <email>brh4008@med.cornell.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Weill Cornell Medicine/NewYork-Presbyterian Hospital</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Tejasvi Kaur Sahni</last_name>
        <email>tks4001@med.cornell.edu</email>
      </contact>
      <contact_backup>
        <last_name>Brittany Hobbie</last_name>
        <email>brh4008@med.cornell.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Samuel Yamshon, M.D.</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Mosunetuzumab</keyword>
    <keyword>Follicular Lymphoma</keyword>
    <keyword>Tazemetostat</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Lymphoma, Follicular</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05994235
  org study id: 23-06026184
  secondary id: 22-10025285
  nct id: NCT05994235
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this study is to learn about the safety and effectiveness of the combination of
        tazemetostat pills in combination with mosunetuzumab injections for people with follicular
        lymphoma who haven't received treatment before. The investigators hypothesize that
        tazemetostat with mosunetuzumab has the potential to increase the efficacy of the product
        without compromising the safety.
  
        Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell
        lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and
        enhance the immune system's ability to fight it. Tazemetostat is FDA-approved in previously
        treated follicular lymphoma and currently undergoing study in other lymphomas.
  
        Mosunetuzumab is a bispecific antibody therapy that is a therapeutic strategy that uses the
        immune system to fight lymphoma, called immunotherapy. Bispecific antibodies have two ends:
        one attaches to T cells in the immune system and the other attaches to lymphoma cells,
        helping guide our immune system to attack the cancer. Mosunetuzumab has been studied in
        follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is
        approved by the FDA to be given intravenously (directly into a vein) but is not yet approved
        by the FDA is not yet approved as an injection under the skin, which is how it is given in
        this study. They have not yet been studied in combination.
  This is a phase II, open-label study. Fifty patients with previously untreated follicular
        lymphoma will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and
        with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning
        at the same time as mosunetuzumab initiation. Mosunetuzumab and tazemetostat will be given in
        28-day cycles for up to 12 cycles. Response assessments by PET/CT will occur at 12 weeks
        post-mosunetuzumab and again at 30 and 48 weeks for those with an ongoing response to
        treatment. Treatment with steroids, tocilizumab, growth factors, tumor lysis prophylaxis, and
        antibiotics may be used as per standard of care at our institution. Dose modifications are
        permitted for toxicity. There will be a follow-up visit after 2 years from starting the
        study.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of participants who achieve a complete response (CR) by completion of therapy, as determined by the Lugano Criteria
  time frame: Estimated day 336
  description: The proportion of patients who achieve complete response as per the Lugano criteria will be calculated and their 90% confidences will be computed with Clopper-Pearson method via exact binomial distribution.
  measure: Number of participants who experience cytokine release syndrome (CRS)
  time frame: Day 0 to Day 28
  description: CRS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading
  measure: Number of participants who experience Immune effector cell-associated neurotoxicity syndrome (ICANS)
  time frame: Day 0 to Day 28
  description: ICANS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading
  measure: Median Progression-Free Survival (PFS)
  time frame: For a maximum of approximately 10 years
  description: PFS is defined as the duration of time from start of treatment to time of progression or death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.
  measure: Median Overall Survival (OS)
  time frame: For a maximum of approximately 10 years
  description: OS is defined as the duration of time from start of treatment to death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.
  measure: Objective Response Rate (ORR) at the time of therapy completion, as defined by Lugano Criteria
  time frame: Estimated to be day 336
  description: ORR is defined as the proportion of patients who have a partial or complete response to therapy
  measure: Number of participants who achieve a Complete Response (CR) per Lugano's Criteria
  time frame: For a maximum of approximately 10 years
  description: Response and progression are evaluated according to the Lugano criteria for lymphoma response.
  measure: Median Duration of Response
  time frame: For a maximum of approximately 10 years
  description: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease or death due to any cause, whichever occurs first is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
  arm group label: Subcutaneous Mosunetuzumab and Oral Tazemetostat
  arm group type: Experimental
  description: 50 patients will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation.
  intervention type: Drug
  intervention name: Mosunetuzumab
  description: Mosunetuzumab will be administered in weekly dose increments ("step-up dosing") during Cycle 1 and then on Day 1 of each cycle. Mosunetuzumab will be given in 28-day cycles for up to 12 cycles. Mosunetuzumab will be administered SC at the dose of 5 mg on Day 1, 45 mg on Day 8, and 45 mg on Day 15 in Cycle 1. Beginning with Cycle 2, it will be administered SC at the dose of 45 mg on Day 1. Each cycle lasts 4 weeks.
  arm group label: Subcutaneous Mosunetuzumab and Oral Tazemetostat
  intervention type: Drug
  intervention name: Tazemetostat Pill
  description: Oral tazemetostat will be administered by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation until disease progression, unacceptable toxicity, or consent is withdrawn. Patients will remain on tazemetostat for up to twelve 28-day cycles from initiation of mosunetuzumab.
  arm group label: Subcutaneous Mosunetuzumab and Oral Tazemetostat
  other name: Tazverik
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Samuel Yamshon, M.D.
  role: Principal Investigator
  affiliation: Weill Medical College of Cornell University
  last name: Tejasvi Kaur Sahni
  phone: 646-962-9337
  email: tks4001@med.cornell.edu
  last name: Brittany Hobbie
  email: brh4008@med.cornell.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Lymphoma, Follicular
  sharing ipd: No