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/NCT05996185</url>
    </required_header>
    <id_info>
      <org_study_id>2000031871</org_study_id>
      <nct_id>NCT05996185</nct_id>
    </id_info>
    <brief_title>Study of Mogamulizumab With DA-EPOCH in Patients With Aggressive T Cell Lymphoma</brief_title>
    <official_title>Phase II Study of Mogamulizumab With DA-EPOCH in Patients With Aggressive T Cell Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tarsheen Sethi</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Kyowa Kirin, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Yale 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>
        Single- arm Phase II study evaluating the combination of mogamulizumab (MOGA) added on top of&#xD;
        standard of care dose adjusted EPOCH (DA-EPOCH) in patients with newly diagnosed or&#xD;
        relapsed/refractory (for CTCL only) aggressive T cell lymphoma including patients with Adult&#xD;
        T-cell leukemia/lymphoma (ATLL).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single arm, open label, multicenter phase 2 study of DA-EPOCH and Mogamulizumab in&#xD;
        patients with newly diagnosed or relapsed/refractory (for CTCL only) aggressive T-cell&#xD;
        lymphomas including ATLL and transformed Mycosis Fungoides/Sézary syndrome (MF/SS). The&#xD;
        hypothesis is that this combination is effective and will produce a CR rate of 80%. DA-EPOCH&#xD;
        and Mogamulizumab will be administered for 6 cycles and depending on the histology,&#xD;
        consolidative strategies including SCT will be considered. Response assessments will occur at&#xD;
        pre-specified intervals. Dose adjustments for specific toxicities with drugs are detailed in&#xD;
        the protocol. Based on statistical analysis, a maximum of 36 patients will need to be accrued&#xD;
        to evaluate for disease response based on historical control.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">August 2027</completion_date>
    <primary_completion_date type="Anticipated">August 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab&#xD;
  Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1.&#xD;
  Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Complete response after 6 cycles of treatment with the combination Mogamulizumab and standard of care DA-EPOCH</measure>
      <time_frame>6 cycles (126 Days)</time_frame>
      <description>As assessed by the Lugano criteria for PTCL(16)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Complete response after 6 cycles of treatment with the combination Mogamulizumab and standard of care DA-EPOCH</measure>
      <time_frame>6 cycles (126 Days)</time_frame>
      <description>As assessed by the global response score for CTCL(17)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Occurrence of toxicity</measure>
      <time_frame>2 years</time_frame>
      <description>As assessed by the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) for grading</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression free survival (PFS)</measure>
      <time_frame>2 years</time_frame>
      <description>Defined as the time from enrollment to earliest of progression, death or follow-up</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>2 years</time_frame>
      <description>Defined as the time from enrollment to death or last follow-up</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response</measure>
      <time_frame>2 Years</time_frame>
      <description>Defined as the interval from response initiation to progression or death, whichever occurs first</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to best response</measure>
      <time_frame>2 years</time_frame>
      <description>Defined as the time from treatment initiation to best response</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>T Cell Lymphoma</condition>
    <arm_group>
      <arm_group_label>Mogamulizumab + DA-EPOCH</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab&#xD;
  Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1.&#xD;
  Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH&#xD;
  Mogamulizumab will be administered modified to a 21-day cycle in combination with chemotherapy. Subjects will receive 1.0 mg/kg of mogamulizumab as an IV infusion over at least 1 hour on Days 1, 8, 15 of the first cycle and Day 1 for the subsequent cycles. This dosing regimen will ensure the first 4 doses are given weekly at a dose of 1 mg/kg. Subsequent dosing will occur on a 21-day schedule to coincide with the frequency of administration of DA-EPOCH to allow for simpler co-administration of the study drugs.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mogamulizumab</intervention_name>
      <description>Mogamulizumab is a humanized monoclonal antibody directed against C-C chemokine receptor 4 (CCR4) with potential anti-inflammatory and antineoplastic activities. Mogamulizumab selectively binds to and blocks the activity of CCR4, which may inhibit CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, and chemokine-mediated angiogenesis.</description>
      <arm_group_label>Mogamulizumab + DA-EPOCH</arm_group_label>
      <other_name>Poteligeo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>DA-EPOCH Protocol</intervention_name>
      <description>EPOCH is an intensive chemotherapy regimen intended for treatment of aggressive non-Hodgkin's lymphoma.</description>
      <arm_group_label>Mogamulizumab + DA-EPOCH</arm_group_label>
      <other_name>dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male/female patients who are at least 18 years of age on the day of signing informed&#xD;
               consent with histologically confirmed diagnosis of T-cell Non-Hodgkin lymphoma (T-NHL)&#xD;
               will be enrolled in this study.&#xD;
  &#xD;
            2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 unless compromised&#xD;
               by lymphoma with anticipated benefit from chemotherapy as determined and documented by&#xD;
               the investigator.&#xD;
  &#xD;
            3. Histologically confirmed T-cell Non-Hodgkin lymphoma (T-NHL), including but not&#xD;
               limited to:&#xD;
  &#xD;
                 -  Peripheral T-cell lymphoma not otherwise specified (PTCL nos)&#xD;
  &#xD;
                 -  Angioimmunoblastic T-cell lymphoma (AITL)&#xD;
  &#xD;
                 -  Anaplastic large-cell lymphoma (ALCL)&#xD;
  &#xD;
                 -  Cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF)/sezary&#xD;
                    syndrome patients for whom multi-agent chemotherapy is indicated&#xD;
  &#xD;
                 -  Transformed mycosis fungoides/Sezary syndrome&#xD;
  &#xD;
                 -  Enteropathy-associated T-cell lymphoma (EATL)&#xD;
  &#xD;
                 -  Subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)&#xD;
  &#xD;
                 -  Hepatosplenic T- cell lymphomas&#xD;
  &#xD;
                 -  Gamma delta T cell lymphomas&#xD;
  &#xD;
                 -  Adult T-cell lymphoma leukemia (ATLL)&#xD;
  &#xD;
                 -  T-prolymphocytic leukemia with nodal or visceral involvement&#xD;
  &#xD;
            4. Prior therapy- patients with aggressive T cell lymphoma may have received one cycle of&#xD;
               CHOP, CHOEP or EPOCH before enrollment, if necessary, to control the disease.&#xD;
  &#xD;
            5. For patients with peripheral T-cell lymphoma (PTCL): At least one measurable target&#xD;
               lesion ≥ 1.5 cm&#xD;
  &#xD;
            6. A female patient is eligible to participate if she is not pregnant, not breastfeeding,&#xD;
               and at least one of the following conditions applies:&#xD;
  &#xD;
                 -  Not a woman of childbearing potential (WOCBP) OR&#xD;
  &#xD;
                 -  A woman of childbearing potential (WOCBP) - must have a negative serum or urine&#xD;
                    pregnancy test during screening and must agree to follow instructions for using&#xD;
                    acceptable contraception (Appendix 5) from the time of signing consent, and at&#xD;
                    least 180 days (6 months) after her final dose of mogamulizumab.&#xD;
  &#xD;
            7. A male patient must agree to use a contraception as detailed in Appendix 5 of this&#xD;
               protocol during the treatment period and for at least at least 180 days (6 months)&#xD;
               after her final dose of mogamulizumab and refrain from donating sperm during this&#xD;
               period.&#xD;
  &#xD;
            8. Adequate organ and bone marrow function resulted ≤ 10 days prior to first dose of&#xD;
               protocol-indicated treatment unless compromised by disease involvement of bone marrow,&#xD;
               spleen, or liver as determined and documented by the investigator.&#xD;
  &#xD;
            9. Patients previously treated with anti-CD4 antibody or alemtuzumab are eligible&#xD;
               provided their CD4+ cell counts are ≥ 200/mm.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Has received prior systemic anti-cancer therapy including investigational agents ≤ 3&#xD;
               weeks prior to first dose of study treatment on Cycle 1, Day 1. Skin directed&#xD;
               treatments, including topicals and radiation within 2 weeks of study treatment.&#xD;
               However, patients with rapidly progressive malignant disease may be enrolled prior to&#xD;
               this period after discussion with the sponsor investigator.&#xD;
  &#xD;
            2. Has received radiotherapy within 2 weeks of start of study treatment. Patients must&#xD;
               have recovered from all radiation-related toxicities, and not have had radiation&#xD;
               pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of&#xD;
               radiotherapy) to non-CNS disease.&#xD;
  &#xD;
            3. If patient received major surgery, they must have recovered adequately from the&#xD;
               toxicity and/or complications from the intervention prior to starting study treatment.&#xD;
  &#xD;
            4. Patients on any immunomodulatory drug for concomitant or intercurrent conditions other&#xD;
               than T-cell lymphoma or who have received any of these agents within 4 weeks of&#xD;
               treatment, including but not limited to the following, will be excluded: low dose or&#xD;
               oral methotrexate; azathioprine; iv immunoglobulin; low dose or oral cyclophosphamide;&#xD;
               cyclosporine; mycophenolate; infliximab; etanercept; leflunomide; adalimumab;&#xD;
               lenalidomide; abatacept; rituximab; anakinra; interferon-β; IL-2 and natalizumab. .&#xD;
               Concurrent use of topical steroids or therapies for CTCL is allowed as indicated in&#xD;
               the protocol.&#xD;
  &#xD;
            5. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test&#xD;
               within 72 hours of treatment start. If the urine test is positive or cannot be&#xD;
               confirmed as negative, a serum pregnancy test will be required.&#xD;
  &#xD;
            6. Has received a live vaccine within 30 days prior to the first dose of study drug.&#xD;
               Examples of live vaccines include, but are not limited to, the following: measles,&#xD;
               mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus&#xD;
               Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection&#xD;
               are generally killed virus vaccines and are allowed; however, intranasal influenza&#xD;
               vaccines (eg,FluMist®) are live attenuated vaccines and are not allowed.&#xD;
  &#xD;
            7. Is currently participating in or has participated in a study of an investigational&#xD;
               agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
               study treatment.&#xD;
  &#xD;
               Note: Patients who have entered the follow-up phase of an investigational study may&#xD;
               participate as long as it has been 4 weeks after the last dose of the previous&#xD;
               investigational agent.&#xD;
  &#xD;
            8. Active uncontrolled infection requiring systemic therapy (patients must be afebrile&#xD;
               for ≥ 48 hours and off antibiotics prior to treatment). If fever is attributed to&#xD;
               tumor fever (B symptom) then these criteria would not apply.&#xD;
  &#xD;
            9. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA)&#xD;
               functional classification III-IV heart failure.&#xD;
  &#xD;
           10. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously&#xD;
               treated brain metastases may participate provided they are radiologically stable, i.e.&#xD;
               without evidence of progression for at least 4 weeks by repeat imaging (note that the&#xD;
               repeat imaging should be performed during study screening), clinically stable and&#xD;
               without requirement of steroid treatment for at least 14 days prior to first dose of&#xD;
               study treatment.&#xD;
  &#xD;
           11. Diagnosed with a malignancy, not treated under the study (hormonal therapy for breast&#xD;
               or prostate cancer excepted), in the past 2 years. However, patients with non-&#xD;
               melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current&#xD;
               prostate-specific antigen of &lt; 0.1 ng/mL, treated thyroid cancer or cervical carcinoma&#xD;
               in situ or ductal/lobular carcinoma in situ of the breast with in the past 2 years may&#xD;
               enroll as long as there is no current evidence of disease.&#xD;
  &#xD;
           12. Known severe hypersensitivity (≥Grade 3) to mogamulizumab and/or any of its excipients&#xD;
               and /or EPOCH or any of its excipients.&#xD;
  &#xD;
           13. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is&#xD;
               required unless mandated by local health authority.&#xD;
  &#xD;
           14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]&#xD;
               reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is&#xD;
               detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required&#xD;
               unless mandated by local health authority.&#xD;
  &#xD;
           15. Known psychiatric or substance abuse disorders that would interfere with cooperation&#xD;
               with the requirements of the trial.&#xD;
  &#xD;
           16. Has a known history of active TB (Bacillus Tuberculosis).&#xD;
  &#xD;
           17. Prior allogeneic stem cell transplant within last 2 years or active graft vs. host&#xD;
               disease (GVHD).&#xD;
  &#xD;
           18. Known active autoimmune disease will be excluded if the disease requires active&#xD;
               medical treatment. (For example, Graves' disease; systemic lupus erythematosus;&#xD;
               rheumatoid arthritis; Crohn's disease; psoriasis).&#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>Tarsheen Sethi</last_name>
      <role>Principal Investigator</role>
      <affiliation>Yale University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Maxime Oriol</last_name>
      <phone>2037856497</phone>
      <email>maxime.oriol@yale.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Julie Holub</last_name>
      <email>Julie.holub@yale.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Yale Smilow Cancer Hospital</name>
        <address>
          <city>New Haven</city>
          <state>Connecticut</state>
          <zip>06510</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Kylie Boyhen</last_name>
        <phone>203-752-7835</phone>
        <email>kylie.boyhen@yale.edu</email>
      </contact>
      <investigator>
        <last_name>Tarsheen Sethi, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Bazarbachi A, Suarez F, Fields P, Hermine O. How I treat adult T-cell leukemia/lymphoma. Blood. 2011 Aug 18;118(7):1736-45. doi: 10.1182/blood-2011-03-345702. Epub 2011 Jun 14.</citation>
      <PMID>21673346</PMID>
    </reference>
    <reference>
      <citation>Ellin F, Landstrom J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014 Sep 4;124(10):1570-7. doi: 10.1182/blood-2014-04-573089. Epub 2014 Jul 8.</citation>
      <PMID>25006130</PMID>
    </reference>
    <reference>
      <citation>Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illes A, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Huttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trumper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. doi: 10.1016/S0140-6736(18)32984-2. Epub 2018 Dec 4. Erratum In: Lancet. 2019 Jan 19;393(10168):228.</citation>
      <PMID>30522922</PMID>
    </reference>
    <reference>
      <citation>Mehta N, Maragulia JC, Moskowitz A, Hamlin PA, Lunning MA, Moskowitz CH, Zelenetz A, Matasar MJ, Sauter C, Goldberg J, Horwitz SM. A retrospective analysis of peripheral T-cell lymphoma treated with the intention to transplant in the first remission. Clin Lymphoma Myeloma Leuk. 2013 Dec;13(6):664-70. doi: 10.1016/j.clml.2013.07.005. Epub 2013 Sep 11.</citation>
      <PMID>24035712</PMID>
    </reference>
    <reference>
      <citation>Maeda Y, Nishimori H, Yoshida I, Hiramatsu Y, Uno M, Masaki Y, Sunami K, Masunari T, Nawa Y, Yamane H, Gomyo H, Takahashi T, Yano T, Matsuo K, Ohshima K, Nakamura S, Yoshino T, Tanimoto M. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017 Dec;102(12):2097-2103. doi: 10.3324/haematol.2017.167742. Epub 2017 Sep 29.</citation>
      <PMID>28971899</PMID>
    </reference>
    <reference>
      <citation>Toriyama E, Imaizumi Y, Taniguchi H, Taguchi J, Nakashima J, Itonaga H, Sato S, Ando K, Sawayama Y, Hata T, Fukushima T, Miyazaki Y. EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma. Int J Hematol. 2018 Aug;108(2):167-175. doi: 10.1007/s12185-018-2455-x. Epub 2018 Apr 12.</citation>
      <PMID>29651666</PMID>
    </reference>
    <reference>
      <citation>Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L, Morris S, Kim EJ, Ortiz-Romero PL, Eradat H, Scarisbrick J, Tsianakas A, Elmets C, Dalle S, Fisher DC, Halwani A, Poligone B, Greer J, Fierro MT, Khot A, Moskowitz AJ, Musiek A, Shustov A, Pro B, Geskin LJ, Dwyer K, Moriya J, Leoni M, Humphrey JS, Hudgens S, Grebennik DO, Tobinai K, Duvic M; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018 Sep;19(9):1192-1204. doi: 10.1016/S1470-2045(18)30379-6. Epub 2018 Aug 9. Erratum In: Lancet Oncol. 2018 Nov;19(11):e581.</citation>
      <PMID>30100375</PMID>
    </reference>
    <reference>
      <citation>Zinzani PL, Karlin L, Radford J, Caballero D, Fields P, Chamuleau ME, d'Amore F, Haioun C, Thieblemont C, Gonzalez-Barca E, Garcia CG, Johnson PW, van Imhoff GW, Ng T, Dwyer K, Morschhauser F. European phase II study of mogamulizumab, an anti-CCR4 monoclonal antibody, in relapsed/refractory peripheral T-cell lymphoma. Haematologica. 2016 Oct;101(10):e407-e410. doi: 10.3324/haematol.2016.146977. Epub 2016 Jul 14. No abstract available.</citation>
      <PMID>27418646</PMID>
    </reference>
    <reference>
      <citation>Jo T, Matsuzaka K, Shioya H, Tominaga H, Sakai T, Kaneko Y, Hayashi S, Matsuo M, Taguchi J, Abe K, Shigematsu K, Kubota-Koketsu R. Mogamulizumab Plus EPOCH Therapy for Patients With Newly Diagnosed Aggressive Adult T-cell Leukemia/lymphoma. Anticancer Res. 2020 Sep;40(9):5237-5243. doi: 10.21873/anticanres.14527.</citation>
      <PMID>32878812</PMID>
    </reference>
    <reference>
      <citation>Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. doi: 10.1111/bjh.13338. Epub 2015 Mar 2.</citation>
      <PMID>25733162</PMID>
    </reference>
    <reference>
      <citation>Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. doi: 10.1182/blood.v99.8.2685.</citation>
      <PMID>11929754</PMID>
    </reference>
    <reference>
      <citation>Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y, Miyamoto T, Takemoto S, Suzushima H, Tsukasaki K, Nosaka K, Fujiwara H, Ishitsuka K, Inagaki H, Ogura M, Akinaga S, Tomonaga M, Tobinai K, Ueda R. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012 Mar 10;30(8):837-42. doi: 10.1200/JCO.2011.37.3472. Epub 2012 Feb 6.</citation>
      <PMID>22312108</PMID>
    </reference>
    <reference>
      <citation>Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y, Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010 Mar 20;28(9):1591-8. doi: 10.1200/JCO.2009.25.3575. Epub 2010 Feb 22.</citation>
      <PMID>20177026</PMID>
    </reference>
    <reference>
      <citation>Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.</citation>
      <PMID>25113753</PMID>
    </reference>
    <reference>
      <citation>Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, Wood GS, Willemze R, Demierre MF, Pimpinelli N, Bernengo MG, Ortiz-Romero PL, Bagot M, Estrach T, Guitart J, Knobler R, Sanches JA, Iwatsuki K, Sugaya M, Dummer R, Pittelkow M, Hoppe R, Parker S, Geskin L, Pinter-Brown L, Girardi M, Burg G, Ranki A, Vermeer M, Horwitz S, Heald P, Rosen S, Cerroni L, Dreno B, Vonderheid EC; International Society for Cutaneous Lymphomas; United States Cutaneous Lymphoma Consortium; Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. Clinical end points and response criteria in mycosis fungoides and Sezary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. J Clin Oncol. 2011 Jun 20;29(18):2598-607. doi: 10.1200/JCO.2010.32.0630. Epub 2011 May 16.</citation>
      <PMID>21576639</PMID>
    </reference>
    <reference>
      <citation>Byford ET, Carr M, Ladikou E, Ahearne MJ, Wagner SD. Circulating Tfh1 (cTfh1) cell numbers and PD1 expression are elevated in low-grade B-cell non-Hodgkin's lymphoma and cTfh gene expression is perturbed in marginal zone lymphoma. PLoS One. 2018 Jan 2;13(1):e0190468. doi: 10.1371/journal.pone.0190468. eCollection 2018.</citation>
      <PMID>29293620</PMID>
    </reference>
    <reference>
      <citation>Leelatian N, Diggins KE, Irish JM. Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry. Methods Mol Biol. 2015;1346:99-113. doi: 10.1007/978-1-4939-2987-0_8.</citation>
      <PMID>26542718</PMID>
    </reference>
    <reference>
      <citation>Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.</citation>
      <PMID>7165009</PMID>
    </reference>
    <reference>
      <citation>Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.</citation>
      <PMID>1244564</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Yale University</investigator_affiliation>
      <investigator_full_name>Tarsheen Sethi</investigator_full_name>
      <investigator_title>MD, MSCI, Assistant Professor of Medicine</investigator_title>
    </responsible_party>
    <keyword>Relapsed</keyword>
    <keyword>Refractory</keyword>
    <keyword>Adult T-Cell Leukemia/Lymphoma</keyword>
    <keyword>Cutaneous T-cell lymphoma</keyword>
    <keyword>Mycosis Fungoides/Sézary syndrome</keyword>
    <keyword>DA-EPOCH</keyword>
    <keyword>Mogamulizumab</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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Prednisone</mesh_term>
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Doxorubicin</mesh_term>
      <mesh_term>Etoposide</mesh_term>
      <mesh_term>Vincristine</mesh_term>
      <mesh_term>Mogamulizumab</mesh_term>
    </intervention_browse>
    <!-- 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/NCT05996185
  org study id: 2000031871
  nct id: NCT05996185
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  Single- arm Phase II study evaluating the combination of mogamulizumab (MOGA) added on top of
        standard of care dose adjusted EPOCH (DA-EPOCH) in patients with newly diagnosed or
        relapsed/refractory (for CTCL only) aggressive T cell lymphoma including patients with Adult
        T-cell leukemia/lymphoma (ATLL).
  This is a single arm, open label, multicenter phase 2 study of DA-EPOCH and Mogamulizumab in
        patients with newly diagnosed or relapsed/refractory (for CTCL only) aggressive T-cell
        lymphomas including ATLL and transformed Mycosis Fungoides/Sézary syndrome (MF/SS). The
        hypothesis is that this combination is effective and will produce a CR rate of 80%. DA-EPOCH
        and Mogamulizumab will be administered for 6 cycles and depending on the histology,
        consolidative strategies including SCT will be considered. Response assessments will occur at
        pre-specified intervals. Dose adjustments for specific toxicities with drugs are detailed in
        the protocol. Based on statistical analysis, a maximum of 36 patients will need to be accrued
        to evaluate for disease response based on historical control.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab
  Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1.
  Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Complete response after 6 cycles of treatment with the combination Mogamulizumab and standard of care DA-EPOCH
  time frame: 6 cycles (126 Days)
  description: As assessed by the Lugano criteria for PTCL(16)
  measure: Complete response after 6 cycles of treatment with the combination Mogamulizumab and standard of care DA-EPOCH
  time frame: 6 cycles (126 Days)
  description: As assessed by the global response score for CTCL(17)
  measure: Occurrence of toxicity
  time frame: 2 years
  description: As assessed by the NCI Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) for grading
  measure: Progression free survival (PFS)
  time frame: 2 years
  description: Defined as the time from enrollment to earliest of progression, death or follow-up
  measure: Overall survival (OS)
  time frame: 2 years
  description: Defined as the time from enrollment to death or last follow-up
  measure: Duration of response
  time frame: 2 Years
  description: Defined as the interval from response initiation to progression or death, whichever occurs first
  measure: Time to best response
  time frame: 2 years
  description: Defined as the time from treatment initiation to best response
  arm group label: Mogamulizumab + DA-EPOCH
  arm group type: Experimental
  description: All subjects are scheduled to receive six cycles of DA-EPOCH + Mogamulizumab
  Cycle 1: Mogamulizumab on days 1,8,15, of a 21-day cycle with DA-EPOCH on day 1.
  Cycle 2 onwards: Mogamulizumab on day 1 with DA-EPOCH
  Mogamulizumab will be administered modified to a 21-day cycle in combination with chemotherapy. Subjects will receive 1.0 mg/kg of mogamulizumab as an IV infusion over at least 1 hour on Days 1, 8, 15 of the first cycle and Day 1 for the subsequent cycles. This dosing regimen will ensure the first 4 doses are given weekly at a dose of 1 mg/kg. Subsequent dosing will occur on a 21-day schedule to coincide with the frequency of administration of DA-EPOCH to allow for simpler co-administration of the study drugs.
  intervention type: Drug
  intervention name: Mogamulizumab
  description: Mogamulizumab is a humanized monoclonal antibody directed against C-C chemokine receptor 4 (CCR4) with potential anti-inflammatory and antineoplastic activities. Mogamulizumab selectively binds to and blocks the activity of CCR4, which may inhibit CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, and chemokine-mediated angiogenesis.
  arm group label: Mogamulizumab + DA-EPOCH
  other name: Poteligeo
  intervention type: Drug
  intervention name: DA-EPOCH Protocol
  description: EPOCH is an intensive chemotherapy regimen intended for treatment of aggressive non-Hodgkin's lymphoma.
  arm group label: Mogamulizumab + DA-EPOCH
  other name: dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Tarsheen Sethi
  role: Principal Investigator
  affiliation: Yale University
  last name: Maxime Oriol
  phone: 2037856497
  email: maxime.oriol@yale.edu
  last name: Julie Holub
  email: Julie.holub@yale.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  citation: Bazarbachi A, Suarez F, Fields P, Hermine O. How I treat adult T-cell leukemia/lymphoma. Blood. 2011 Aug 18;118(7):1736-45. doi: 10.1182/blood-2011-03-345702. Epub 2011 Jun 14.
  PMID: 21673346
  citation: Ellin F, Landstrom J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014 Sep 4;124(10):1570-7. doi: 10.1182/blood-2014-04-573089. Epub 2014 Jul 8.
  PMID: 25006130
  citation: Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illes A, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Huttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trumper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. doi: 10.1016/S0140-6736(18)32984-2. Epub 2018 Dec 4. Erratum In: Lancet. 2019 Jan 19;393(10168):228.
  PMID: 30522922
  citation: Mehta N, Maragulia JC, Moskowitz A, Hamlin PA, Lunning MA, Moskowitz CH, Zelenetz A, Matasar MJ, Sauter C, Goldberg J, Horwitz SM. A retrospective analysis of peripheral T-cell lymphoma treated with the intention to transplant in the first remission. Clin Lymphoma Myeloma Leuk. 2013 Dec;13(6):664-70. doi: 10.1016/j.clml.2013.07.005. Epub 2013 Sep 11.
  PMID: 24035712
  citation: Maeda Y, Nishimori H, Yoshida I, Hiramatsu Y, Uno M, Masaki Y, Sunami K, Masunari T, Nawa Y, Yamane H, Gomyo H, Takahashi T, Yano T, Matsuo K, Ohshima K, Nakamura S, Yoshino T, Tanimoto M. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017 Dec;102(12):2097-2103. doi: 10.3324/haematol.2017.167742. Epub 2017 Sep 29.
  PMID: 28971899
  citation: Toriyama E, Imaizumi Y, Taniguchi H, Taguchi J, Nakashima J, Itonaga H, Sato S, Ando K, Sawayama Y, Hata T, Fukushima T, Miyazaki Y. EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma. Int J Hematol. 2018 Aug;108(2):167-175. doi: 10.1007/s12185-018-2455-x. Epub 2018 Apr 12.
  PMID: 29651666
  citation: Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, Tokura Y, Vermeer M, Zinzani PL, Sokol L, Morris S, Kim EJ, Ortiz-Romero PL, Eradat H, Scarisbrick J, Tsianakas A, Elmets C, Dalle S, Fisher DC, Halwani A, Poligone B, Greer J, Fierro MT, Khot A, Moskowitz AJ, Musiek A, Shustov A, Pro B, Geskin LJ, Dwyer K, Moriya J, Leoni M, Humphrey JS, Hudgens S, Grebennik DO, Tobinai K, Duvic M; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018 Sep;19(9):1192-1204. doi: 10.1016/S1470-2045(18)30379-6. Epub 2018 Aug 9. Erratum In: Lancet Oncol. 2018 Nov;19(11):e581.
  PMID: 30100375
  citation: Zinzani PL, Karlin L, Radford J, Caballero D, Fields P, Chamuleau ME, d'Amore F, Haioun C, Thieblemont C, Gonzalez-Barca E, Garcia CG, Johnson PW, van Imhoff GW, Ng T, Dwyer K, Morschhauser F. European phase II study of mogamulizumab, an anti-CCR4 monoclonal antibody, in relapsed/refractory peripheral T-cell lymphoma. Haematologica. 2016 Oct;101(10):e407-e410. doi: 10.3324/haematol.2016.146977. Epub 2016 Jul 14. No abstract available.
  PMID: 27418646
  citation: Jo T, Matsuzaka K, Shioya H, Tominaga H, Sakai T, Kaneko Y, Hayashi S, Matsuo M, Taguchi J, Abe K, Shigematsu K, Kubota-Koketsu R. Mogamulizumab Plus EPOCH Therapy for Patients With Newly Diagnosed Aggressive Adult T-cell Leukemia/lymphoma. Anticancer Res. 2020 Sep;40(9):5237-5243. doi: 10.21873/anticanres.14527.
  PMID: 32878812
  citation: Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. doi: 10.1111/bjh.13338. Epub 2015 Mar 2.
  PMID: 25733162
  citation: Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. doi: 10.1182/blood.v99.8.2685.
  PMID: 11929754
  citation: Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y, Miyamoto T, Takemoto S, Suzushima H, Tsukasaki K, Nosaka K, Fujiwara H, Ishitsuka K, Inagaki H, Ogura M, Akinaga S, Tomonaga M, Tobinai K, Ueda R. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012 Mar 10;30(8):837-42. doi: 10.1200/JCO.2011.37.3472. Epub 2012 Feb 6.
  PMID: 22312108
  citation: Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y, Hanada S, Tamura K, Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M, Ueda R. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010 Mar 20;28(9):1591-8. doi: 10.1200/JCO.2009.25.3575. Epub 2010 Feb 22.
  PMID: 20177026
  citation: Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800.
  PMID: 25113753
  citation: Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, Wood GS, Willemze R, Demierre MF, Pimpinelli N, Bernengo MG, Ortiz-Romero PL, Bagot M, Estrach T, Guitart J, Knobler R, Sanches JA, Iwatsuki K, Sugaya M, Dummer R, Pittelkow M, Hoppe R, Parker S, Geskin L, Pinter-Brown L, Girardi M, Burg G, Ranki A, Vermeer M, Horwitz S, Heald P, Rosen S, Cerroni L, Dreno B, Vonderheid EC; International Society for Cutaneous Lymphomas; United States Cutaneous Lymphoma Consortium; Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. Clinical end points and response criteria in mycosis fungoides and Sezary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. J Clin Oncol. 2011 Jun 20;29(18):2598-607. doi: 10.1200/JCO.2010.32.0630. Epub 2011 May 16.
  PMID: 21576639
  citation: Byford ET, Carr M, Ladikou E, Ahearne MJ, Wagner SD. Circulating Tfh1 (cTfh1) cell numbers and PD1 expression are elevated in low-grade B-cell non-Hodgkin's lymphoma and cTfh gene expression is perturbed in marginal zone lymphoma. PLoS One. 2018 Jan 2;13(1):e0190468. doi: 10.1371/journal.pone.0190468. eCollection 2018.
  PMID: 29293620
  citation: Leelatian N, Diggins KE, Irish JM. Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry. Methods Mol Biol. 2015;1346:99-113. doi: 10.1007/978-1-4939-2987-0_8.
  PMID: 26542718
  citation: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
  PMID: 7165009
  citation: Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
  PMID: 1244564
  responsible party type: Sponsor-Investigator
  investigator affiliation: Yale University
  investigator full name: Tarsheen Sethi
  investigator title: MD, MSCI, Assistant Professor of Medicine
  mesh term: Lymphoma
  mesh term: Lymphoma, T-Cell
  mesh term: Lymphoma, T-Cell, Peripheral
  mesh term: Prednisone
  mesh term: Cyclophosphamide
  mesh term: Doxorubicin
  mesh term: Etoposide
  mesh term: Vincristine
  mesh term: Mogamulizumab