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/NCT05983965</url>
    </required_header>
    <id_info>
      <org_study_id>IRB-300011353</org_study_id>
      <nct_id>NCT05983965</nct_id>
    </id_info>
    <brief_title>Study of Tazemetostat in Lymphoid Malignancies</brief_title>
    <official_title>Phase I Study to Evaluate Safety and Tolerability of Tazemetostat in Relapsed/Refractory Peripheral T-cell Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Alabama at Birmingham</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Alabama at Birmingham</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Tazemetostat is an oral EZH2 inhibitor which has been FDA approved for adult patients with&#xD;
        relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2&#xD;
        mutation as detected by an FDA-approved test and who have received at least 2 prior systemic&#xD;
        therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment&#xD;
        option. We propose a study to evaluate the safety of tazemetostat in relapsed / refractory&#xD;
        peripheral T-cell lymphoma.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">December 2029</completion_date>
    <primary_completion_date type="Anticipated">December 2027</primary_completion_date>
    <phase>Phase 1</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>Identify the recommended phase II dose of Tazemetostat</measure>
      <time_frame>28 days</time_frame>
      <description>The measurement will be the occurrence of a dose limiting toxicity (DLT) in the first cycle (28 days) after treatment initiation from the start of cycle 1 day 1.&#xD;
  Measurements will be graded on a Hematologic Toxicity scale from grades 1 through 4 with grade 4 being worst grade.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>T-cell Lymphoma</condition>
    <arm_group>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>T-cell Lymphomas</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tazemetostat</intervention_name>
      <description>Treatment: On day 1 and day 15 of the first cycle, and day 1 of all following cycles, the subject will have office visit with physical exam, vital signs, and lab tests. The subject will take tazemetostat twice a day by mouth continuously as an outpatient. If continuing on the treatment for more than 6 cycles, visits change to every 3 months.</description>
      <arm_group_label>Cohort A</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria&#xD;
  &#xD;
            1. Histologically confirmed peripheral T-cell lymphomas (PTCL) with allowed subtypes&#xD;
               listed below as per the revised World Health Organization 2022 classification [6]:&#xD;
  &#xD;
               PTCL subtypes allowed&#xD;
  &#xD;
                 1. PTCL-not otherwise specified (NOS)&#xD;
  &#xD;
                 2. Nodal T-follicular helper cell lymphoma - angioimmunoblastic type, follicular&#xD;
                    type, or NOS&#xD;
  &#xD;
                 3. Anaplastic Large Cell Lymphoma (ALK+)&#xD;
  &#xD;
                 4. Anaplastic Large Cell Lymphoma (ALK-)&#xD;
  &#xD;
                 5. Enteropathy-associated T-cell lymphoma&#xD;
  &#xD;
                 6. Monomorphic epitheliotropic intestinal T-cell lymphoma&#xD;
  &#xD;
                 7. Hepatosplenic T-cell lymphoma&#xD;
  &#xD;
                 8. Subcutaneous panniculitis-like T-cell lymphoma&#xD;
  &#xD;
                 9. Adult T-cell leukemia / lymphoma - lymphomatous, acute, or unfavorable chronic&#xD;
                    subtypes&#xD;
  &#xD;
            2. Patients must have relapsed or refractory disease.&#xD;
  &#xD;
                 1. Relapsed disease is defined when a patient progressed (&gt;3 months) after achieving&#xD;
                    CR with a previous treatment&#xD;
  &#xD;
                 2. Refractory disease is defined when a patient failed to achieve a CR or PR after a&#xD;
                    previous treatment&#xD;
  &#xD;
            3. Patients received at least 1 prior therapy for PTCL.&#xD;
  &#xD;
            4. At least one bi-dimensionally measurable nodal lesion, defined as ≥ 1.5 cm in its&#xD;
               longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as ≥&#xD;
               1.0 cm in its longest diameter on fluorodeoxyglucose (FDG) positron emission&#xD;
               tomography (PET)/computed tomography (CT) scan as defined by response criteria for&#xD;
               PTCL&#xD;
  &#xD;
            5. Age ≥ 18.&#xD;
  &#xD;
            6. Patients with Hepatitis C can be included if they have completed therapy for hepatitis&#xD;
               C with undetectable viral load.&#xD;
  &#xD;
            7. Patients with Hepatitis B can be included if they are on suppressive therapy for&#xD;
               hepatitis B infection and with no detectable viral load.&#xD;
  &#xD;
            8. Patients with HIV can be included if they are on appropriate antiretroviral therapy,&#xD;
               there is no interaction with the study drug, a CD4+ T-cell counts ≥ 350 cells/µL and&#xD;
               no detectable viral load.&#xD;
  &#xD;
            9. Adequate organ function as defined below unless attributed to disease involvement&#xD;
               (Note: transfusions and growth factors allowed during screening; however,&#xD;
               transfusion-dependency defined as requiring blood products ≥once per week not&#xD;
               allowed):&#xD;
  &#xD;
               i. Liver function: No more than moderate hepatic impairment per NCI ODWG criteria -&#xD;
               Total bilirubin ≤ 3X upper limit of normal (ULN), AST ≤ ULN (unless attributed to&#xD;
               fatty liver or disease involvement).&#xD;
  &#xD;
               ii. Kidney function: CrCl &gt; 30ml/min using Cockroft-Gault, based on actual weight.&#xD;
  &#xD;
               iii. ANC ≥ 1,000/µL, Platelet Count ≥ 75,000/ µL, Hemoglobin ≥ 8.0 g/dl.&#xD;
  &#xD;
           10. Left ventricular ejection fraction (LVEF) defined by multiple-gated acquisition (MUGA)&#xD;
               scan or echocardiogram within the institutional limits of normal.&#xD;
  &#xD;
           11. Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2.&#xD;
  &#xD;
           12. A negative urine or serum pregnancy test is required for all women of childbearing&#xD;
               potential within 1 week prior to enrolling on this trial and within 3 days of first&#xD;
               dose of study drug. Note: Urine pregnancy tests that cannot be confirmed as negative&#xD;
               require a confirmatory negative serum pregnancy test.&#xD;
  &#xD;
               Non-childbearing potential is defined as:&#xD;
  &#xD;
                 -  Postmenopausal: Defined as no menses for 12 months without an alternative medical&#xD;
                    cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal&#xD;
                    range may be used to confirm post-menopausal state in women not using hormonal&#xD;
                    contraception or hormonal replacement therapy. In the absence of 12 months of&#xD;
                    amenorrhea, FSH measurements indicating post-menopausal status must be documented&#xD;
                    in patient's medical history.&#xD;
  &#xD;
                 -  Permanently sterile: Documented permanent sterilization e.g., hysterectomy,&#xD;
                    bilateral salpingectomy and bilateral oophorectomy.&#xD;
  &#xD;
           13. If female of childbearing potential, subject must not be pregnant or be breastfeeding&#xD;
               and is required to have a negative urine or serum pregnancy test within 3 days prior&#xD;
               to the first dose of study drug. In addition, females of childbearing potential must&#xD;
               either practice complete abstinence or agree to use two effective methods of&#xD;
               contraception simultaneously, beginning ≥ 28 days prior to start of tazemetostat,&#xD;
               during tazemetostat treatment, and for at least 6 months after final dose of&#xD;
               tazemetostat. See Appendix E regarding contraception guidelines.&#xD;
  &#xD;
           14. Male subjects must either practice complete abstinence or agree to use a latex or&#xD;
               synthetic condom during any sexual contact with a female of childbearing potential,&#xD;
               from first dose of tazemetostat, during study treatment including dose interruptions,&#xD;
               and for 3 months after last dose of tazemetostat. This applies even to males who have&#xD;
               undergone successful vasectomy with medically confirmed azoospermia.&#xD;
  &#xD;
           15. Willing and able to participate in all required evaluations and procedures in this&#xD;
               study protocol including receiving intravenous administration of investigational&#xD;
               product and being admitted, when required, for at least 24 hours during&#xD;
               investigational product administration.&#xD;
  &#xD;
          Exclusion criteria&#xD;
  &#xD;
            1. Current evidence of central nervous system involvement.&#xD;
  &#xD;
            2. Completion of an autologous hematopoietic stem cell transplantation within 3 months&#xD;
               prior to first dose of study drug.&#xD;
  &#xD;
            3. Prior allogeneic stem cell transplant within 6 months. The patient should not have any&#xD;
               active GVH or should be on immune suppressive agents.&#xD;
  &#xD;
            4. Completion of treatment with any radiotherapy, chemotherapy, antibody,&#xD;
               immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of the&#xD;
               drug, whichever is shorter) prior to first dose of study drug. Patients may be&#xD;
               enrolled after a minimum of 2 weeks of radiation if radiation was for palliative&#xD;
               intent.&#xD;
  &#xD;
            5. Prior therapy with an EZH2 inhibitor.&#xD;
  &#xD;
            6. Inability to swallow and retain oral medications.&#xD;
  &#xD;
            7. Pregnant women are excluded from this study.&#xD;
  &#xD;
            8. Any active, concurrent, significant illness or disease (other underlying lymphoma) or&#xD;
               clinically significant findings including psychiatric and behavioral problems, medical&#xD;
               history and/or physical examination findings that would preclude the patient from&#xD;
               participation in the study such as:&#xD;
  &#xD;
               i. Active infection requiring systemic therapy ≤10 days before the first dose of study&#xD;
               drug; ii. Unstable angina pectoris, symptomatic congestive heart failure (New York&#xD;
               Heart Association [NYHA] II, III, IV;), myocardial infarction ≤6 months prior to first&#xD;
               study drug, uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter,&#xD;
               cerebrovascular accidents ≤6 months before first dose of study drug; iii. Any severe&#xD;
               or uncontrolled other disease or condition which might increase the risk associated&#xD;
               with study participation.&#xD;
  &#xD;
            9. Vaccination with live, attenuated vaccines within 28 days prior to the first dose of&#xD;
               study medication.&#xD;
  &#xD;
           10. Receiving systemic immunosuppressive medications (including, but not limited to,&#xD;
               cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis&#xD;
               factor agents). The use of inhaled corticosteroids is permitted.&#xD;
  &#xD;
           11. Corticosteroids ≥ 10 mg of prednisone within the last 7 days.&#xD;
  &#xD;
           12. Has had a solid organ transplant within the last 3 years. Note: Patients who have had&#xD;
               a solid organ transplant &gt;3 years ago are eligible if there are no signs/symptoms of&#xD;
               graft versus host disease (GvHD) and off immunosuppressive medications as per above.&#xD;
  &#xD;
           13. Any prior history of myeloid malignancies, including myelodysplastic syndrome&#xD;
               (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).&#xD;
  &#xD;
           14. Any prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic&#xD;
               leukemia (T-ALL).&#xD;
  &#xD;
           15. Patients with the following subtypes of lymphoma:&#xD;
  &#xD;
               i. T-cell prolymphocytic leukemia ii. T-large granular lymphocytic leukemia iii.&#xD;
               NK-large granular lymphocytic leukemia iv. Aggressive NK-cell leukemia v. Breast&#xD;
               implant-associated anaplastic large-cell lymphoma&#xD;
  &#xD;
           16. Any other malignancy known to be active, with the exception of i. Cervical carcinoma&#xD;
               of Stage 1B or less ii. Non-invasive basal cell or squamous cell skin carcinoma iii.&#xD;
               Non-invasive, superficial bladder cancer iv. Prostate cancer with a current PSA level&#xD;
               &lt; 0.1 ng/mL v. Any curable or localized cancer with a CR of &gt; 2 years' duration.&#xD;
  &#xD;
           17. Any malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg,&#xD;
               nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat.&#xD;
  &#xD;
           18. Major surgery within 4 weeks before the first dose of study intervention. Note: Minor&#xD;
               surgery (eg, minor biopsy of extracranial site, central venous catheter placement,&#xD;
               shunt revision) is permitted within 3 weeks prior to enrolment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Lauren Shea, MD</last_name>
      <phone>205-934-4793</phone>
      <email>lkshea@uabmc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Margaret Thomas, MPH</last_name>
      <email>margaretannthomas@uabmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Alabama at Birmingham</name>
        <address>
          <city>Birmingham</city>
          <state>Alabama</state>
          <zip>35294</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Margaret A Thomas</last_name>
        <email>margaretannthomas@uabmc.edu</email>
      </contact>
      <investigator>
        <last_name>Lauren Shea, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Mayur Narkhede, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Amitkumar Mehta, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
      <investigator_full_name>Lauren Shea</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>T-cell Lymphoma</keyword>
    <keyword>Leukemia</keyword>
    <keyword>Lymphoma</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Lymphoma, T-Cell</mesh_term>
      <mesh_term>Lymphoma, T-Cell, Peripheral</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/NCT05983965
  org study id: IRB-300011353
  nct id: NCT05983965
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  Tazemetostat is an oral EZH2 inhibitor which has been FDA approved for adult patients with
        relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2
        mutation as detected by an FDA-approved test and who have received at least 2 prior systemic
        therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment
        option. We propose a study to evaluate the safety of tazemetostat in relapsed / refractory
        peripheral T-cell lymphoma.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Identify the recommended phase II dose of Tazemetostat
  time frame: 28 days
  description: The measurement will be the occurrence of a dose limiting toxicity (DLT) in the first cycle (28 days) after treatment initiation from the start of cycle 1 day 1.
  Measurements will be graded on a Hematologic Toxicity scale from grades 1 through 4 with grade 4 being worst grade.
  arm group label: Cohort A
  arm group type: Experimental
  description: T-cell Lymphomas
  intervention type: Drug
  intervention name: Tazemetostat
  description: Treatment: On day 1 and day 15 of the first cycle, and day 1 of all following cycles, the subject will have office visit with physical exam, vital signs, and lab tests. The subject will take tazemetostat twice a day by mouth continuously as an outpatient. If continuing on the treatment for more than 6 cycles, visits change to every 3 months.
  arm group label: Cohort A
  criteria: 
  gender: All
  gender based: Yes
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lauren Shea, MD
  phone: 205-934-4793
  email: lkshea@uabmc.edu
  last name: Margaret Thomas, MPH
  email: margaretannthomas@uabmc.edu
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of Alabama at Birmingham
  investigator full name: Lauren Shea
  investigator title: Assistant Professor
  mesh term: Lymphoma
  mesh term: Lymphoma, T-Cell
  mesh term: Lymphoma, T-Cell, Peripheral
  sharing ipd: No