<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/NCT04500561</url>
  </required_header>
  <id_info>
    <org_study_id>YY-20394-008</org_study_id>
    <nct_id>NCT04500561</nct_id>
  </id_info>
  <brief_title>YY-20394 、GEMOX Treatment Diffuse Large B-cell Lymphoma Single Arm, Open, Multicentrized Phase 1b/2 Clinical Trial</brief_title>
  <official_title>YY-20394 Combined With GEMOX in the Treatment of Patients With Relapsed and/or Refractory Diffuse Large B-cell Lymphoma With a Single Arm, Open, Multicentrized Phase 1b/2 Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai YingLi Pharmaceutical Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai YingLi Pharmaceutical Co. Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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 study is a one-arm, open, multicenter phase 1b/2 clinical trial of YY-20394 combined&#xD;
      with GEMOX second-line or above in patients with relapsed and/or refractory diffuse large&#xD;
      B-cell lymphoma.&#xD;
&#xD;
      YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/&#xD;
      day as recommended in phase 2, and the dose of GEMOX was treated according to clinical&#xD;
      standards.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a one-arm, open, multicenter phase 1b/2 clinical trial of YY-20394 combined&#xD;
      with GEMOX second-line or above in patients with relapsed and/or refractory diffuse large&#xD;
      B-cell lymphoma.&#xD;
&#xD;
      YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/&#xD;
      day as recommended in phase 2, and the dose of GEMOX was treated according to clinical&#xD;
      standards.&#xD;
&#xD;
      The first six subjects of group to evaluate the safety of YY - 20394 joint GEMOX, if the&#xD;
      joint treatment of 6 cases of subjects before, If YY-20394 and/or chemotherapy related 4&#xD;
      degrees of hematology toxicity or level 3 non hematologic toxicity were appearanced less than&#xD;
      2 cases, continued to dose of 80 mg/day, if more than 2 cases, YY-20394 doses dropped to 60&#xD;
      mg/day.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 20, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2021</primary_completion_date>
  <phase>Phase 1/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>
    <intervention_model_description>YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of GEMOX was treated according to clinical standards</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>objective remission rate</measure>
    <time_frame>with in 42 days after the first dos</time_frame>
    <description>Response will be determined by the revised International Working Group (IWG 2007) efficacy evaluation criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>disease control rate</measure>
    <time_frame>with in 42 days after the first dos</time_frame>
    <description>Response will be determined by the revised International Working Group (IWG 2007) efficacy evaluation criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>with in 42 days after the first dos</time_frame>
    <description>Response will be determined by the revised International Working Group (IWG 2007) efficacy evaluation criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>drug safety</measure>
    <time_frame>one and half a year</time_frame>
    <description>Adverse events evaluated by NCI CTCAE v5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">28</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>YY-20394</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>YY-20394 tablets will be given daily for 21 days in 21-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>YY-20394</intervention_name>
    <description>Yy-20394 combined with Gemcitabine and Oxaliplatin was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of Gemcitabine and Oxaliplatin was treated according to clinical standards.</description>
    <arm_group_label>YY-20394</arm_group_label>
    <other_name>Gemcitabine</other_name>
    <other_name>Oxaliplatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Patients with recurrent and/or refractory diffuse large B-cell lymphoma confirmed&#xD;
        histologically or cytologically; Progress after first-line or above systemic treatment (at&#xD;
        least CD20 monoclonal antibody treatment); ECOG Performance Status (PS) grade 0 ~ 1;&#xD;
        Expected survival ≥3 months; The patient has at least one measurable lesion conforming to&#xD;
        the IWG2007 standard; Good organ function level:ANC≥1.0×109/L；PLT≥70×109/L；Hb≥80 g/L&#xD;
&#xD;
        ;TBIL≤1.5×ULN； ALT和AST≤2.5×ULN；BUN/Urea和Cr≤1.5×ULN；LVEF≥50%； The Fridericia method&#xD;
        corrected the QT interval (QTcF) for males &lt; 450 ms and females &lt; 470 ms.&#xD;
&#xD;
        From the end of any previous anti-tumor therapy (including radiotherapy, chemotherapy,&#xD;
        hormone therapy, surgery or molecular targeted therapy) to the washout period of this study&#xD;
        ≥4 weeks; Did not participate in the clinical trial as a subject within 1 month before the&#xD;
        trial; According to the researcher's judgment, it can comply with the experimental&#xD;
        protocol; Volunteer to participate in this clinical trial, understand the study procedures&#xD;
        and be able to sign the informed consent in person.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those who have used PI3K as the target of anti-tumor drug progression (except those&#xD;
             who cannot tolerate out of the group); Any other anti-tumor therapy within 4 weeks;&#xD;
             The presence of a third interstitial effusion that cannot be controlled by drainage or&#xD;
             other methods (such as massive pleural and ascites); Use of steroid hormone dosage&#xD;
             (equivalent amount of prednisone) greater than 20mg/ day within 4 weeks, and&#xD;
             continuous use for more than 14 days; Unable to swallow, chronic diarrhea and&#xD;
             intestinal obstruction, existing multiple factors affecting drug intake and&#xD;
             absorption; Unable to suspend medications that may prolong QT interval during the&#xD;
             study (e.g., antiarrhythmic agents); Having lympoma with central nervous system (CNS)&#xD;
             invasion; Allergic constitution, or known anaphylaxis to any component of this&#xD;
             product; Having active viral, bacterial or fungal infection requiring treatment (e.g.,&#xD;
             pneumonia); Uncontrolled diabetes, pulmonary fibrosis, acute pulmonary disease,&#xD;
             interstitial lung disease, or liver failure; Patients with HBV, HCV infection (defined&#xD;
             as HbsAg and/or HbcAb positive and HBV DNA copy number ≥1×104 copy number /ml or ≥2000&#xD;
             IU/ml) or acute or chronic active hepatitis C; Medical history of immunodeficiency,&#xD;
             including HIV testing positive, or having other acquired or congenital&#xD;
             immunodeficiency disease, or history of organ transplantation or allogeneic bone&#xD;
             marrow transplantation; Having received autologous hematopoietic stem cell&#xD;
             transplantation within 90 days prior to the first dose in this study; Any cardiac&#xD;
             disease, including (1) angina pectoris; (2) arrhythmia requiring drug therapy or of&#xD;
             clinical significance; (3) myocardial infarction; (4) heart failure; (5) any other&#xD;
             cardiac disease that is judged by investigators as not suitable to participate in this&#xD;
             trial; Pregnant or lactating women or baseline pregnancy testing positive for fertile&#xD;
             women; Concomitant diseases (such as serious hypertension, diabetes mellitus, thyroid&#xD;
             disease) seriously hazardous to patient's safety or completion of study as judged by&#xD;
             the investigator; Having other primary malignancy in recent 5 years;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhiming Li, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Prevention center affiliated to Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hanying Bao, PHD</last_name>
    <phone>86 21-5137069</phone>
    <email>hybao@yl-pharma.com</email>
  </overall_contact>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>August 3, 2020</last_update_submitted>
  <last_update_submitted_qc>August 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04500561
org study id: YY-20394-008
nct id: NCT04500561
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a one-arm, open, multicenter phase 1b/2 clinical trial of YY-20394 combined
      with GEMOX second-line or above in patients with relapsed and/or refractory diffuse large
      B-cell lymphoma.

      YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/
      day as recommended in phase 2, and the dose of GEMOX was treated according to clinical
      standards.
This study is a one-arm, open, multicenter phase 1b/2 clinical trial of YY-20394 combined
      with GEMOX second-line or above in patients with relapsed and/or refractory diffuse large
      B-cell lymphoma.

      YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/
      day as recommended in phase 2, and the dose of GEMOX was treated according to clinical
      standards.

      The first six subjects of group to evaluate the safety of YY - 20394 joint GEMOX, if the
      joint treatment of 6 cases of subjects before, If YY-20394 and/or chemotherapy related 4
      degrees of hematology toxicity or level 3 non hematologic toxicity were appearanced less than
      2 cases, continued to dose of 80 mg/day, if more than 2 cases, YY-20394 doses dropped to 60
      mg/day.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: YY-20394 combined with GEMOX was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of GEMOX was treated according to clinical standards
primary purpose: Treatment
masking: None (Open Label)
measure: objective remission rate
time frame: with in 42 days after the first dos
description: Response will be determined by the revised International Working Group (IWG 2007) efficacy evaluation criteria
measure: disease control rate
time frame: with in 42 days after the first dos
description: Response will be determined by the revised International Working Group (IWG 2007) efficacy evaluation criteria
measure: Progression Free Survival
time frame: with in 42 days after the first dos
description: Response will be determined by the revised International Working Group (IWG 2007) efficacy evaluation criteria
measure: drug safety
time frame: one and half a year
description: Adverse events evaluated by NCI CTCAE v5.0
arm group label: YY-20394
arm group type: Experimental
description: YY-20394 tablets will be given daily for 21 days in 21-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons
intervention type: Drug
intervention name: YY-20394
description: Yy-20394 combined with Gemcitabine and Oxaliplatin was used as a cycle for 21 days. The dose of YY-20394 was 80mg/ day as recommended in phase 2, and the dose of Gemcitabine and Oxaliplatin was treated according to clinical standards.
arm group label: YY-20394
other name: Gemcitabine
other name: Oxaliplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhiming Li, PHD
role: Principal Investigator
affiliation: Cancer Prevention center affiliated to Sun Yat-sen University
last name: Hanying Bao, PHD
phone: 86 21-5137069
email: hybao@yl-pharma.com
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Gemcitabine
mesh term: Oxaliplatin
sharing ipd: No