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/NCT06018506</url>
    </required_header>
    <id_info>
      <org_study_id>BR108</org_study_id>
      <nct_id>NCT06018506</nct_id>
    </id_info>
    <brief_title>A Phase I Study of BR108 in Hematological Malignancies</brief_title>
    <official_title>A Phase I ,Single-arm, Open-label Study to Evalute the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Clinical Activity of BR108 Injection in Subjects With Hematological Malignancies</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhe Jiang Hisun Bioray Bio-pharmaceu tical Co.Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zhe Jiang Hisun Bioray Bio-pharmaceu tical Co.Ltd</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A Phase I study of BR108 in hematological malignancies&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 27, 2023</start_date>
    <completion_date type="Anticipated">March 2, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 21, 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of Participants with Dose Limiting Toxicity (DLT)</measure>
      <time_frame>up to 28 days</time_frame>
      <description>Dose limiting toxicity</description>
    </primary_outcome>
    <primary_outcome>
      <measure>objective response rate（ORR）</measure>
      <time_frame>up to approximately 3 years</time_frame>
      <description>FOR lymphoma ，Objective Response Rate is defined as the percentage of patients with a complete response (CR) or partial response (PR). For AML, the proportion of participants who achieve a best response of CR, CRi, MLFS, or partial response (PR). For MDS, the proportion of participants who achieve a best response of CR, marrow CR, or PR.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cmax</measure>
      <time_frame>up to approximately 3 years</time_frame>
      <description>Cmax is the maximum observed concentration.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tmax</measure>
      <time_frame>up to approximately 3 years</time_frame>
      <description>Time to maximum concentration attained</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of antidrug antibodies (ADA)</measure>
      <time_frame>up to approximately 3 years</time_frame>
      <description>Percentage of patients producing detectable ADA</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of remission (DOR)</measure>
      <time_frame>up to approximately 3 years</time_frame>
      <description>To preliminarily evaluate DoR in patients with hematological malignancies</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">180</enrollment>
    <condition>Hematologic Malignancy</condition>
    <arm_group>
      <arm_group_label>BR108</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BR108 injection</intervention_name>
      <description>Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle</description>
      <arm_group_label>BR108</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1. Voluntary agreement to provide written informed consent;&#xD;
  &#xD;
            -  2. Males and females who are ≥18 years old;&#xD;
  &#xD;
            -  3. Patients must have an advanced hematologic malignancy including： Relapsed or&#xD;
               refractory lymphoma as defined by World Health Organization(WHO) criteria； Relapsed or&#xD;
               refractory AML /MDSas defined by World Health Organization (WHO) criteria；&#xD;
  &#xD;
            -  4. Subjects must have documented CD70-positive .&#xD;
  &#xD;
            -  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;&#xD;
  &#xD;
            -  7. Expected survival time ≥3 months;&#xD;
  &#xD;
            -  8.Have at least 1 evaluable lesion per Lugano 2014;&#xD;
  &#xD;
            -  9. The function of major organs must meet the following criteria (Lymphoma：have not&#xD;
               received blood transfusion, EPO, G-CSF or other medical supportive treatment within 7&#xD;
               days before the first dose of study drug) ：&#xD;
  &#xD;
                 -  White blood cell count≤25×109/L（for AML/MDS）&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥1.5×109/L or ≥0.75×109 /L for patients with bone&#xD;
                    marrow infiltration, Platelet ≥75×109 /L or ≥50×109 /L for patients with bone&#xD;
                    marrow infiltration; Hemoglobin ≥8.0mmol/L or ≥ 7.0mmol/L for patients with bone&#xD;
                    marrow infiltration;&#xD;
  &#xD;
                 -  International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN; Activated&#xD;
                    Partial Thromboplastin Time (APTT) ≤1.5×ULN;&#xD;
  &#xD;
                 -  serum creatinine≤1.5×ULN or Creatinine clearance rate ≥60 mL/min ;&#xD;
  &#xD;
                 -  Total bilirubin ≤1.5×ULN or ≤3×ULN for patients with Gilbert's syndrome or liver&#xD;
                    metastasis； Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)&#xD;
                    ≤2.5×ULN or ≤5×ULN for patients with liver metastasis:&#xD;
  &#xD;
            -  10. Women of child bearing potential and non-sterilized male patients who are sexually&#xD;
               active with a female partner of child bearing potential must agree to use an effective&#xD;
               method of contraception from screening until 6 months after the last dose of study&#xD;
               drug. Effective methods of contraception consist of prior sterilization, intrauterine&#xD;
               device, intrauterine hormone-releasing system, oral or injectable contraceptives, and&#xD;
               sexual abstinence.&#xD;
  &#xD;
            -  11. Patients will be able to communicate well with the investigator, understand and&#xD;
               comply with the requirements of the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1. Pregnant or lactating women;&#xD;
  &#xD;
            -  2. Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia,&#xD;
               primary central nervous system malignancies or invasion of the central nervous system&#xD;
               (except for those who are asymptomatic or stable and do not require treatment ≥4 weeks&#xD;
               before the first dose of study drug);&#xD;
  &#xD;
            -  3. Has not recovered from adverse reactions caused by previous anti-tumor treatments&#xD;
               to ≤ grade 1 or baseline (refer to NCICTCAE5.0 ), except for alopecia, pigmentation&#xD;
               and other toxicity judged no safety risk by the investigator;&#xD;
  &#xD;
            -  4. Previous exposure to CD70-targeted agents;&#xD;
  &#xD;
            -  5. Patients with Allergic history or hypersensitivity reaction to any components of&#xD;
               BR108 injection;&#xD;
  &#xD;
            -  6. Patients with active bacterial, viral, fungal, mycobacterium, parasite or other&#xD;
               infection (except fungal infection of nail bed) within 7 days prior to enrollment and&#xD;
               requiring intravenous infusion therapy (except neoplastic fever);&#xD;
  &#xD;
            -  7. Patients with inherited or acquired hemorrhagic diseases or severe coagulation&#xD;
               abnormalities of clinical significance（ Such as diffuse intravascular coagulation&#xD;
               (DIC) autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, sickle cell&#xD;
               anemia, etc）;&#xD;
  &#xD;
            -  8. HBsAg or HBcAb positive, and HBV DNA positive; HCVAb positive and HCV RNA positive;&#xD;
               HIV positive; syphilis infection requiring systematic treatment ;&#xD;
  &#xD;
            -  9. Subjects who have received live or attenuated vaccine within 4 weeks before the&#xD;
               first administration or planned to receive live vaccine during the study period;&#xD;
  &#xD;
            -  10. History of any other malignancies within 3 years (except for basal cell carcinoma&#xD;
               of the skin, squamous cell carcinoma of the skin, superficial bladder cancer,&#xD;
               localized prostate cancer, cervical carcinoma in situ, stage I ductal carcinoma in&#xD;
               situ of the breast, and malignancies that have been cured (CR) within 2 years prior to&#xD;
               initial administration and are currently considered stable by the investigator with&#xD;
               minimal risk of recurrence);&#xD;
  &#xD;
            -  11. Patients with serious cardiovascular and cerebrovascular diseases or other serious&#xD;
               organic diseases, including but not limited to:&#xD;
  &#xD;
                 -  History of stroke 、intracranial hemorrhage 、unstable angina pectoris、 congestive&#xD;
                    heart failure (NYHA III-IV)、myocardial infarction、severe arrhythmias (e.g.,&#xD;
                    persistent ventricular tachycardia, ventricular fibrillation) or congenital long&#xD;
                    QT syndrome within 6 months before enrollment.&#xD;
  &#xD;
                 -  Left ventricular ejection fraction （LVEF） &lt; 50% in echocardiography (ECHO) or&#xD;
                    muti-gate detection scan (MUGA) .&#xD;
  &#xD;
                 -  Corrected QT interval prolongation &gt;470ms.&#xD;
  &#xD;
                 -  Patients with interstitial lung disease, severe lung dysfunction, severe&#xD;
                    pulmonary fibrosis, or pulmonary infection requiring systematic treatment.&#xD;
  &#xD;
            -  12. Subjects who have autoimmune disorders and need to rely on immunosuppressive&#xD;
               therapy or receive systemic therapy with a dose of ≥20mg/day of prednisone or other&#xD;
               equivalent hormones within 2 weeks before enrollment;&#xD;
  &#xD;
            -  13. Patients have received other clinical trials within 4 weeks before the first dose&#xD;
               of study drug;&#xD;
  &#xD;
            -  14.Subjects who have major surgery or severe trauma within 4 weeks prior to initial&#xD;
               dosing or plan to take major surgery during the trial period;&#xD;
  &#xD;
            -  15. Treatment with prior anti-cancer therapy (including chemotherapy, endocrine&#xD;
               therapy, targeted therapy, etc.) must have been terminated at last 28 days or 5&#xD;
               half-lives (whichever is shorter) before study enrolment,2 weeks for endocrine therapy&#xD;
               and Chinese medicine treatment with anti-tumor indications or local palliative&#xD;
               radiotherapy for bone metastasis and pain relief within 2 weeks.&#xD;
  &#xD;
            -  16. Prior allogeneic hematopoietic stem cell or organ transplantation; recent&#xD;
               Autologous hematopoietic stem cell transplantation（less than 3 months prior first&#xD;
               dosing of study drug）;&#xD;
  &#xD;
            -  17. Patients with any mental or cognitive impairment that may restrict the&#xD;
               understanding and implementation of the informed consent;&#xD;
  &#xD;
            -  18. Other serious, uncontrollable concomitant diseases that may affect protocol&#xD;
               compliance or interfere with outcomes, or other serious or uncontrollable medical&#xD;
               conditions that the investigator believes may put subjects at risk for participating&#xD;
               in the study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Zhang Huilai, PhD</last_name>
      <phone>18622221228</phone>
      <email>huilaizhangtz@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Tianjin Medical University Cancer Institute and Hospital</name>
        <address>
          <city>Tianjin</city>
          <state>Tianjin</state>
          <zip>300060</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Zhang Huilai, PhD</last_name>
        <phone>18622221228</phone>
        <email>huilaizhangtz@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</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>Neoplasms</mesh_term>
      <mesh_term>Hematologic Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06018506
  org study id: BR108
  nct id: NCT06018506
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  A Phase I study of BR108 in hematological malignancies
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of Participants with Dose Limiting Toxicity (DLT)
  time frame: up to 28 days
  description: Dose limiting toxicity
  measure: objective response rate（ORR）
  time frame: up to approximately 3 years
  description: FOR lymphoma ，Objective Response Rate is defined as the percentage of patients with a complete response (CR) or partial response (PR). For AML, the proportion of participants who achieve a best response of CR, CRi, MLFS, or partial response (PR). For MDS, the proportion of participants who achieve a best response of CR, marrow CR, or PR.
  measure: Cmax
  time frame: up to approximately 3 years
  description: Cmax is the maximum observed concentration.
  measure: Tmax
  time frame: up to approximately 3 years
  description: Time to maximum concentration attained
  measure: Incidence of antidrug antibodies (ADA)
  time frame: up to approximately 3 years
  description: Percentage of patients producing detectable ADA
  measure: Duration of remission (DOR)
  time frame: up to approximately 3 years
  description: To preliminarily evaluate DoR in patients with hematological malignancies
  arm group label: BR108
  arm group type: Experimental
  intervention type: Drug
  intervention name: BR108 injection
  description: Given into the vein (IV; intravenously) on Days 1 and 15 of each treatment cycle
  arm group label: BR108
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Zhang Huilai, PhD
  phone: 18622221228
  email: huilaizhangtz@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Hematologic Neoplasms
  sharing ipd: No