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/NCT05977673</url>
    </required_header>
    <id_info>
      <org_study_id>FIL_Tisle-HL</org_study_id>
      <nct_id>NCT05977673</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of Frontline Tislelizumab in Patients With de Novo Hodgkin Lymphoma Unsuitable for Standard Frontline Chemotherapy</brief_title>
    <acronym>FIL_Tisle-HL</acronym>
    <official_title>Efficacy and Safety of Frontline Tislelizumab in Patients With de Novo Hodgkin Lymphoma Unsuitable for Standard Frontline Chemotherapy: a Phase II, Open-label Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fondazione Italiana Linfomi - ETS</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fondazione Italiana Linfomi - ETS</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a multicenter, prospective, non-randomized, open-label, phase 2 clinical study to&#xD;
        evaluate the efficacy and safety of tislelizumab in patients with de novo Hodgkin Lymphoma&#xD;
        deemed ineligible to frontline chemotherapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Approximately two-thirds of patients with Hodgkin lymphoma (HL) can be cured with standard&#xD;
        frontline chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The&#xD;
        majority of new patients present in the second and third decade of life, but at least 25% of&#xD;
        de novo cases are in patients older than 65. Elderly patients with HL display dismal outcomes&#xD;
        for several reasons: the disease is implicitly more aggressive than in younger adults, with&#xD;
        an advanced stage in at least two-thirds of cases and the presence of multiple risk factors&#xD;
        for poor outcome (according to the International Prognostic Score). Moreover, patients may&#xD;
        show impaired organ function that require chemotherapy dose reductions, treatment delays or&#xD;
        drug withdrawal.&#xD;
  &#xD;
        Given the difficulty of delivering of full treatment doses to elderly patients and to those&#xD;
        with relevant medical comorbidities, there is a need for new and better tolerated agents in&#xD;
        this context.&#xD;
  &#xD;
        Given the difficulty of delivering of full treatment doses to elderly patients and to those&#xD;
        with relevant medical comorbidities, there is a need for new and better tolerated agents in&#xD;
        this context. Importantly, no single agent has received approval for this kind of patients,&#xD;
        and drugs like gemcitabine and bendamustine - both active in relapsed patients with limited&#xD;
        toxicity - have limitations in their prescription. The anti-CD30 immunoconjugate agent&#xD;
        brentuximab vedotin (BV) applied in patients older than 60 years and considered unsuitable&#xD;
        for frontline chemotherapy, yielded an overall response of 92%, with 73% of patients&#xD;
        achieving a complete remission and a median duration of response of 9.1 months.&#xD;
  &#xD;
        Immune checkpoint inhibitors, namely nivolumab and pembrolizumab, have been largely tested in&#xD;
        patients with relapsed and refractory HL failing both autologous stem cell transplant and BV.&#xD;
        Both agents display efficacy in this context, with significant rates of objective responses,&#xD;
        which appear to be durable. Along with an acceptable safety profile, both agents have been&#xD;
        approved in relapsed and refractory HL, providing a good treatment option for heavily&#xD;
        pretreated patients. Tislelizumab (T, BGB-A317) is a humanized IgG4 mAb with high affinity&#xD;
        and specificity for programmed cell death protein 1 (PD1), showing a superior antitumor&#xD;
        activity compared to nivolumab in mice transplanted with human cancer cells and peripheral&#xD;
        blood mononuclear cells. High response rates have been reported in Chinese HL patients who&#xD;
        have failed or were ineligible to autologous transplantation, including a complete response&#xD;
        rate of 61% and a partial response rate of 24%.&#xD;
  &#xD;
        Investigators postulate that an induction based on single-agent tislelizumab can be a&#xD;
        feasible chemo-free treatment strategy to be offered to patients with de novo HL who are&#xD;
        unsuitable for a chemotherapy-based frontline approach.&#xD;
  &#xD;
        The study also addresses biological evaluation of biomarkers in the tumor clone and in the&#xD;
        microenvironment at baseline and their possible correlation with patients' outcome and&#xD;
        responses.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">April 2029</completion_date>
    <primary_completion_date type="Anticipated">April 2027</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>Overall Response Rate (CR + PR)</measure>
      <time_frame>From treatment start up to about 24 months</time_frame>
      <description>The primary endpoint of the study is the ORR (the sum of complete response (CR) and partial response (PR) rate).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DoR)</measure>
      <time_frame>Between +33 days after treatment start up to 66 months</time_frame>
      <description>Time from first documented complete response according to Lugano and LYRIC criteria to disease relapse.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>From registration up to 66 months</time_frame>
      <description>Time from registration to the earliest date of documentation of disease progression, relapse or death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>From registration up to 66 months</time_frame>
      <description>Time from registration to death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease free survival (DFS)</measure>
      <time_frame>Between +33 days after treatment start up to 66 months</time_frame>
      <description>Time from first documented complete response according to Lugano and LYRIC criteria to disease relapse or death as a result of lymphoma or acute toxicity of treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of adverse events during and up to 90 days after treatment</measure>
      <time_frame>From treatment start up to 66 months</time_frame>
      <description>To evaluate the safety and tolerability of tislelizumab</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Hodgkin Lymphoma</condition>
    <arm_group>
      <arm_group_label>Tislelizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Tislelizumab single dose every 3 weeks up to 35 total administration</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tislelizumab</intervention_name>
      <description>Tislelizumab 200mg IV day1</description>
      <arm_group_label>Tislelizumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Histologically confirmed diagnosis of de novo classical Hodgkin Lymphoma (cHL). Note:&#xD;
               Availability of either block or unstained slides plus stained slides used by the local&#xD;
               pathologist to make diagnosis, and of all pathology reports is mandatory for the study&#xD;
               to perform central pathology review for confirmation of cHL diagnosis and for&#xD;
               biological biomarkers assessments. Central pathology confirmation is not required to&#xD;
               start treatment;&#xD;
  &#xD;
            -  Age &gt;= 65 years OR ineligibility for frontline standard chemotherapy (mainly due to&#xD;
               medical comorbidities), provided the patient is &gt;= 18 years old;&#xD;
  &#xD;
            -  Treatment naïve;&#xD;
  &#xD;
            -  Measurable disease defined as presence of both fluorodeoxyglucose-avid nodal&#xD;
               involvement and at least one nodal target lesion measurable in two diameters (and at&#xD;
               least 1.5 cm in its major diameter); • Indication for systemic treatment, i.e., all&#xD;
               stages except IA without a large tumor burden, as radiotherapy is regarded curative in&#xD;
               those patients;&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) &lt;= 2;&#xD;
  &#xD;
            -  Adequate organ and marrow function as defined below:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) &gt; 109/L (without growth factor support within 7&#xD;
                    days of ANC measurement), unless due to bone marrow involvement by lymphoma&#xD;
  &#xD;
                 -  Platelet &gt; 50 x 109/L (without growth factor support or transfusion within 7 days&#xD;
                    of platelets measurement) , unless due to bone marrow involvement by lymphoma&#xD;
  &#xD;
                 -  Hemoglobin &gt; 8 g/dL (prior transfusion is acceptable)&#xD;
  &#xD;
                 -  Creatinine clearance ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or&#xD;
                    as measured by nuclear medicine scan or 24-hour urine collection)&#xD;
  &#xD;
                 -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and&#xD;
                    alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper&#xD;
                    limit of normal (ULN)&#xD;
  &#xD;
                 -  Serum total bilirubin &lt; 1.5 × ULN (or &lt; 3 x ULN in case of documented Gilbert's&#xD;
                    syndrome)&#xD;
  &#xD;
            -  Life expectancy ≥ 6 months;&#xD;
  &#xD;
            -  Women of childbearing potential (WOCBP) and men must agree to use effective&#xD;
               contraception if sexually active. This applies for the time period between signing of&#xD;
               the informed consent form and 4 months after last tislelizumab dose. A woman is&#xD;
               considered of childbearing potential, i.e., fertile, following menarche and until&#xD;
               becoming postmenopausal unless permanently sterile. Permanent sterilization methods&#xD;
               include but are not limited to hysterectomy, bilateral salpingectomy and bilateral&#xD;
               oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months&#xD;
               without an alternative medical cause. A high follicle stimulating hormone (FSH) level&#xD;
               in the postmenopausal range may be used to confirm a postmenopausal state in women not&#xD;
               using hormonal contraception or hormonal replacement therapy. The investigator or a&#xD;
               designated associate is requested to advise the patient how to achieve highly&#xD;
               effective birth control method (failure rate of less than 1%) e.g., intrauterine&#xD;
               device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion,&#xD;
               vasectomized partner. The use of condoms by male patients is required unless the&#xD;
               female partner is permanently sterile. Otherwise, they must agree to practice complete&#xD;
               sexual abstinence, when this is in line with the preferred and usual lifestyle of the&#xD;
               subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post&#xD;
               ovulation methods for the female partner] and withdrawal are not acceptable methods of&#xD;
               contraception) WOCBP must have a negative pregnancy test as verified by the study&#xD;
               doctor prior to starting study therapy and must agree to undergo pregnancy testing&#xD;
               during the course of the study, and after end of study therapy. This applies even if&#xD;
               the subject practices complete abstinence from heterosexual contact.&#xD;
  &#xD;
            -  Subject voluntarily signs and dates an informed consent form approved by an National&#xD;
               Ethics Committee (NEC) prior to the initiation of any screening or study-specific&#xD;
               procedures, indicating that they understand the purpose of and procedures required for&#xD;
               the study and are willing to participate in it;&#xD;
  &#xD;
            -  Subject must be able to adhere to the study visit schedule and other protocol&#xD;
               requirements, and to return to enrolling institution for follow-up (during the active&#xD;
               monitoring phase of the study).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Nodular lymphocyte predominant HL;&#xD;
  &#xD;
            -  Any previous treatment (including radiation therapy) for HL;&#xD;
  &#xD;
            -  Any active autoimmune disease requiring systemic treatment (including&#xD;
               disease-modifying agents, corticosteroids, immunosuppressants) in the past 2 years;&#xD;
               Note: Patients with the following diseases are not excluded and may proceed to further&#xD;
               screening: Type I diabetes under control; Hypothyroidism (provided it is managed with&#xD;
               hormone replacement therapy only); Controlled celiac disease;&#xD;
  &#xD;
            -  Has known history of interstitial lung disease, non-infectious pneumonitis, pulmonary&#xD;
               fibrosis, acute lung diseases or evidence of dyspnea at rest or pulse oximetry of &lt;&#xD;
               92% while breathing room air;&#xD;
  &#xD;
            -  A history of previous exposure to anti-PD1, anti-PDL1 or anti-PDL2 or anti-CTLA-4&#xD;
               agents for any disease other than HL;&#xD;
  &#xD;
            -  Use of systemic treatment with either corticosteroids (&gt; 10 mg daily prednisone&#xD;
               equivalents) or other immunosuppressive medications ≤14 days from registration; Note:&#xD;
               Inhaled or topical steroids and adrenal replacement doses &gt; 10 mg daily prednisone&#xD;
               equivalents are permitted in the absence of active autoimmune disease;&#xD;
  &#xD;
            -  Known infection with HIV, human T-cell lymphotropic virus-1, -2; • Serologic status&#xD;
               reflecting active hepatitis B defined as presence of hepatitis B surface antigen&#xD;
               (HBsAg) or hepatitis B core antibody (HBcAb) (mandatory testing). Patients with occult&#xD;
               or prior HBV infection (respectively defined as patient with HBsAg-/HBcAb+ and&#xD;
               patients HBsAg+ with HBV DNA undetectable) are eligible, provided that they are&#xD;
               willing to undergo prophylactic antiviral medication according to local standard of&#xD;
               care. Patients who have protective titers of hepatitis B surface antibody (HBsAb)&#xD;
               after vaccination are eligible;&#xD;
  &#xD;
            -  Presence of hepatitis C virus (HCV) antibody (mandatory HCV antibody serology&#xD;
               testing). Patients with presence of HCV antibody are eligible only if PCR is negative&#xD;
               for HCV RNA;&#xD;
  &#xD;
            -  Hypersensitivity to tislelizumab or any of its excipients;&#xD;
  &#xD;
            -  Active central nervous system (CNS) involvement or leptomeningeal metastases&#xD;
               involvement;&#xD;
  &#xD;
            -  Evidence of other clinically significant uncontrolled and/or active systemic infection&#xD;
               (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;&#xD;
  &#xD;
            -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment&#xD;
               of the investigator, would make the patient inappropriate for entry into this study or&#xD;
               interfere significantly with the proper assessment of safety and toxicity of the&#xD;
               prescribed regimens;&#xD;
  &#xD;
            -  Pregnant or breastfeeding women;&#xD;
  &#xD;
            -  Major surgery within 4 weeks of the first dose of study drug;&#xD;
  &#xD;
            -  Vaccination with a live vaccine within 4 weeks prior to the first dose of study drug;&#xD;
  &#xD;
            -  Clinically significant cardiovascular disease including the following:&#xD;
  &#xD;
                 -  Myocardial infarction within 6 months before screening;&#xD;
  &#xD;
                 -  Unstable angina within 3 months before screening;&#xD;
  &#xD;
                 -  New York Heart Association Classification III or IV congestive heart failure;&#xD;
  &#xD;
                 -  History of clinically significant arrhythmias (e.g., sustained ventricular&#xD;
                    tachycardia, ventricular fibrillation, torsade de pointes);&#xD;
  &#xD;
                 -  QTcF &gt; 480 msecs based on Fridericia's formula;&#xD;
  &#xD;
                 -  History of Mobitz II second-degree or third-degree heart block without a&#xD;
                    permanent pacemaker in place;&#xD;
  &#xD;
                 -  Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood&#xD;
                    pressure measurements showing systolic blood pressure &gt; 170 mm Hg and diastolic&#xD;
                    blood pressure &gt; 105 mm Hg at screening;&#xD;
  &#xD;
            -  Significant history of neurologic, psychiatric, endocrinological, metabolic,&#xD;
               immunologic, or hepatic disease that would preclude participation in the study or&#xD;
               compromise ability to give informed consent;&#xD;
  &#xD;
            -  Any history of other active malignancies within 3 years prior to study entry, with the&#xD;
               exception of adequately treated in situ carcinoma of the cervix uterine, basal cell&#xD;
               carcinoma of the skin or localized squamous cell carcinoma of the skin, previous&#xD;
               malignancy confined and surgically resected with curative intent;&#xD;
  &#xD;
            -  History of severe hypersensitivity reactions to other monoclonal antibodies;&#xD;
  &#xD;
            -  Concurrent participation in another therapeutic clinical trial.&#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>Pier Luigi Zinzani, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Istituto di Ematologia &quot;L. e A. Seràgnoli&quot;, AOU Policlinico S.Orsola-Malpighi, Bologna</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Uffici Studi FIL</last_name>
      <phone>+390131033153</phone>
      <email>startup@filinf.it</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Uffici Studi FIL</last_name>
      <phone>+390599769913</phone>
      <email>gestionestudi@filinf.it</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>A.O. SS. Antonio e Biagio e Cesare Arrigo, S.C. Ematologia</name>
        <address>
          <city>Alessandria</city>
          <state>IT</state>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Manuela Zanni, MD</last_name>
        <email>manuela.zanni@ospedale.al.it</email>
      </contact>
      <investigator>
        <last_name>Manuela Zanni, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Divisione di Oncologia e dei Tumori immuto-correlati, Centro Di Riferimento Oncologico Di Aviano</name>
        <address>
          <city>Aviano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Michele Spina, MD</last_name>
        <email>mspina@cro.it</email>
      </contact>
      <investigator>
        <last_name>Michele Spina, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Istituto di Ematologia L. e A. Seràgnoli, AOU Policlinico S. Orsola-Malpighi</name>
        <address>
          <city>Bologna</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Pier Luigi Zinzani, MD</last_name>
        <email>pierluigi.zinzani@unibo.it</email>
      </contact>
      <investigator>
        <last_name>Pier Luigi Zinzani, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>SC Ematologia, Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia</name>
        <address>
          <city>Brescia</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Alessandra Tucci, MD</last_name>
        <email>alessandra.tucci@asst-spedalicivili.it</email>
      </contact>
      <investigator>
        <last_name>Alessandra Tucci, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Ematologia, Fondazione IRCCS Istituto Nazionale Dei Tumori</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Chiara Rusconi, MD</last_name>
        <email>chiara.rusconi@istitutotumori.mi.it</email>
      </contact>
      <investigator>
        <last_name>Chiara Rusconi, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Unità di Ematologia e TMO - Unità Linfomi, Ospedale San Raffaele</name>
        <address>
          <city>Milano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrés J.M. Ferreri, MD</last_name>
        <email>andres.ferreri@hsr.it</email>
      </contact>
      <investigator>
        <last_name>Andrés J.M. Ferreri, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Oncologia, IRCCS Istituto Nazionale Tumori Fondazione Pascale</name>
        <address>
          <city>Napoli</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Antonio Pinto, MD</last_name>
        <email>a.pinto@istitutotumori.na.it</email>
      </contact>
      <investigator>
        <last_name>Antonio Pinto, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Oncoematologia, Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello</name>
        <address>
          <city>Palermo</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Caterina Patti, MD</last_name>
        <email>k.patti@villasofia.it</email>
      </contact>
      <investigator>
        <last_name>Caterina Patti, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione, Azienda Ospealiero Universitaria Policlinico Umberto I</name>
        <address>
          <city>Roma</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Ilaria Del Giudice, MD</last_name>
        <email>ilaria.delgiudice@uniroma1.it</email>
      </contact>
      <investigator>
        <last_name>Ilaria Del Giudice, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>U.O di Oncologia Medica ed Ematologia, Humanitas Research Hospital</name>
        <address>
          <city>Rozzano</city>
          <country>Italy</country>
        </address>
      </facility>
      <contact>
        <last_name>Francesca Ricci, MD</last_name>
        <email>francesca.ricci@humanitas.it</email>
      </contact>
      <investigator>
        <last_name>Francesca Ricci, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Lymphoma</keyword>
    <keyword>Hodgkin</keyword>
    <keyword>Tislelizumab</keyword>
    <keyword>PD1</keyword>
    <keyword>Checkpoint</keyword>
    <keyword>Inhibitor</keyword>
    <keyword>De novo</keyword>
    <keyword>Unsuitable</keyword>
    <keyword>Chemotherapy</keyword>
    <keyword>Immune</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
      <mesh_term>Hodgkin Disease</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tislelizumab</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/NCT05977673
  org study id: FIL_Tisle-HL
  nct id: NCT05977673
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, prospective, non-randomized, open-label, phase 2 clinical study to
        evaluate the efficacy and safety of tislelizumab in patients with de novo Hodgkin Lymphoma
        deemed ineligible to frontline chemotherapy.
  Approximately two-thirds of patients with Hodgkin lymphoma (HL) can be cured with standard
        frontline chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The
        majority of new patients present in the second and third decade of life, but at least 25% of
        de novo cases are in patients older than 65. Elderly patients with HL display dismal outcomes
        for several reasons: the disease is implicitly more aggressive than in younger adults, with
        an advanced stage in at least two-thirds of cases and the presence of multiple risk factors
        for poor outcome (according to the International Prognostic Score). Moreover, patients may
        show impaired organ function that require chemotherapy dose reductions, treatment delays or
        drug withdrawal.
  
        Given the difficulty of delivering of full treatment doses to elderly patients and to those
        with relevant medical comorbidities, there is a need for new and better tolerated agents in
        this context.
  
        Given the difficulty of delivering of full treatment doses to elderly patients and to those
        with relevant medical comorbidities, there is a need for new and better tolerated agents in
        this context. Importantly, no single agent has received approval for this kind of patients,
        and drugs like gemcitabine and bendamustine - both active in relapsed patients with limited
        toxicity - have limitations in their prescription. The anti-CD30 immunoconjugate agent
        brentuximab vedotin (BV) applied in patients older than 60 years and considered unsuitable
        for frontline chemotherapy, yielded an overall response of 92%, with 73% of patients
        achieving a complete remission and a median duration of response of 9.1 months.
  
        Immune checkpoint inhibitors, namely nivolumab and pembrolizumab, have been largely tested in
        patients with relapsed and refractory HL failing both autologous stem cell transplant and BV.
        Both agents display efficacy in this context, with significant rates of objective responses,
        which appear to be durable. Along with an acceptable safety profile, both agents have been
        approved in relapsed and refractory HL, providing a good treatment option for heavily
        pretreated patients. Tislelizumab (T, BGB-A317) is a humanized IgG4 mAb with high affinity
        and specificity for programmed cell death protein 1 (PD1), showing a superior antitumor
        activity compared to nivolumab in mice transplanted with human cancer cells and peripheral
        blood mononuclear cells. High response rates have been reported in Chinese HL patients who
        have failed or were ineligible to autologous transplantation, including a complete response
        rate of 61% and a partial response rate of 24%.
  
        Investigators postulate that an induction based on single-agent tislelizumab can be a
        feasible chemo-free treatment strategy to be offered to patients with de novo HL who are
        unsuitable for a chemotherapy-based frontline approach.
  
        The study also addresses biological evaluation of biomarkers in the tumor clone and in the
        microenvironment at baseline and their possible correlation with patients' outcome and
        responses.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall Response Rate (CR + PR)
  time frame: From treatment start up to about 24 months
  description: The primary endpoint of the study is the ORR (the sum of complete response (CR) and partial response (PR) rate).
  measure: Duration of response (DoR)
  time frame: Between +33 days after treatment start up to 66 months
  description: Time from first documented complete response according to Lugano and LYRIC criteria to disease relapse.
  measure: Progression-free survival (PFS)
  time frame: From registration up to 66 months
  description: Time from registration to the earliest date of documentation of disease progression, relapse or death from any cause.
  measure: Overall survival (OS)
  time frame: From registration up to 66 months
  description: Time from registration to death from any cause.
  measure: Disease free survival (DFS)
  time frame: Between +33 days after treatment start up to 66 months
  description: Time from first documented complete response according to Lugano and LYRIC criteria to disease relapse or death as a result of lymphoma or acute toxicity of treatment.
  measure: Incidence and severity of adverse events during and up to 90 days after treatment
  time frame: From treatment start up to 66 months
  description: To evaluate the safety and tolerability of tislelizumab
  arm group label: Tislelizumab
  arm group type: Experimental
  description: Tislelizumab single dose every 3 weeks up to 35 total administration
  intervention type: Drug
  intervention name: Tislelizumab
  description: Tislelizumab 200mg IV day1
  arm group label: Tislelizumab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Pier Luigi Zinzani, MD
  role: Principal Investigator
  affiliation: Istituto di Ematologia "L. e A. Seràgnoli", AOU Policlinico S.Orsola-Malpighi, Bologna
  last name: Uffici Studi FIL
  phone: +390131033153
  email: startup@filinf.it
  last name: Uffici Studi FIL
  phone: +390599769913
  email: gestionestudi@filinf.it
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  facility: 
  contact: 
  investigator: 
  country: Italy
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Hodgkin Disease
  mesh term: Tislelizumab