<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/NCT04457869</url>
  </required_header>
  <id_info>
    <org_study_id>NTP-F520-003</org_study_id>
    <nct_id>NCT04457869</nct_id>
  </id_info>
  <brief_title>A Study of F520 in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Secondary Central Nervous System Lymphoma (SCNSL)</brief_title>
  <official_title>A Phase 2, Open-label, Single-arm, Multicenter Study of F520 in Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Secondary Central Nervous System Lymphoma (SCNSL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shandong New Time Pharmaceutical Co., LTD</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shandong New Time Pharmaceutical Co., LTD</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>
      It is a multi-center, prospective, open-label, two-stage optimized design, single-arm, phase&#xD;
      II clinical study to evaluate the efficacy and safety of F520 for the treatment of&#xD;
      Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Secondary Central&#xD;
      Nervous System Lymphoma (SCNSL).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2020</start_date>
  <completion_date type="Anticipated">January 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2022</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>
    <intervention_model_description>F520</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR) by Independent Review Committee (IRC) Independent Review Committee (IRC).</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Response assessment will be performed according to modified IPCG response. criteria on contrastenhanced cranial MRI-scans.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) based on the investigator assessment.</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Response assessment will be performed according to modified IPCG response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Based on IRC and the investigator assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Based on IRC and the investigator assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of F520</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>AE/SAE will be assessed by CTCAE v5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">43</enrollment>
  <condition>Primary Central Nervous System Lymphoma</condition>
  <condition>Secondary Central Nervous System Lymphoma</condition>
  <arm_group>
    <arm_group_label>Single arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F520</intervention_name>
    <description>3mg/kg every 3 weeks</description>
    <arm_group_label>Single arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female of 18 Years and older;&#xD;
&#xD;
          2. Pathologically confirmed PCNSL or SCNSL of primary testicular diffuse large B-cell&#xD;
             lymphoma (PT-DLBCL) who failed or did not respond to at least 1 line of systemic&#xD;
             therapy; Recurrence and refractory should meet the following definitions:&#xD;
&#xD;
               -  PCNSL patients: relapse is defined as the appearance of new lesions at the&#xD;
                  primary site or other sites after the standard treatment with MTX reaches&#xD;
                  complete remission (CR). Refractory patients were defined as those who did not&#xD;
                  reach PR in 2 cycles or CR in 4 cycles after standard treatment with MTX. If the&#xD;
                  best effect or end cause was PD, the number of courses was not required;&#xD;
&#xD;
               -  patients with SCNSL: Patients with relapsed/refractory primary testicular diffuse&#xD;
                  large B-cell lymphoma who must include central nervous system invasion. Relapse&#xD;
                  was defined as the patients who had been prevented or treated with MTX;&#xD;
                  refractory was defined as the patients who had received the latest chemotherapy&#xD;
                  regimen for 2 cycles without PR or 4 cycles without CR. if the best effect or end&#xD;
                  cause was PD, the number of courses was not required;&#xD;
&#xD;
          3. Measurable disease requirements on scans: subjects should have at least one measurable&#xD;
             extranodal brain lesion more than 10×10mm;&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0~2;&#xD;
&#xD;
          5. Agree to provide archived tumor tissue specimens or fresh tissue specimens;&#xD;
&#xD;
          6. Life expectancy ≥ 3 months;&#xD;
&#xD;
          7. Adequate laboratory parameters during the screening period as evidenced by the&#xD;
             following（No blood components and cell growth factors are allowed within 14 days prior&#xD;
             to screening）:&#xD;
&#xD;
             routine blood tests: Absolute neutrophil count ≥1.5×109/L ;Platelets&#xD;
             ≥100×109/L;Hemoglobin ≥ 9.0 g/dL; Liver function：Total bilirubin (TBIL) ≤1.5×upper&#xD;
             limit of normal (ULN), ALT and AST ≤2.5ULN; for subjects with liver metastases,&#xD;
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5×ULN, Total&#xD;
             bilirubin (TBIL) ≤3×upper limit of normal (ULN); Renal function CCr≤1.5×ULN，Creatinine&#xD;
             clearance≥50 mL/min; Thyroid function indicators: thyroid-stimulating hormone (TSH)&#xD;
             and free thyroxine (FT3/FT4) are within the normal range or no clinical significant;&#xD;
&#xD;
          8. International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit&#xD;
             of normal;&#xD;
&#xD;
          9. Understand study procedures and contents, and voluntarily sign the written informed&#xD;
             consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. a）Patients with suspected or existing eye tumors; b）patients who cannot undergo MRI&#xD;
             assessments c) PCNSL patients with systemic disease;&#xD;
&#xD;
          2. Patients with certain diseases such as active autoimmune disease, type I diabetes,&#xD;
             hypothyroidism that needs hormone replacement, active infection, psychiatric disorder&#xD;
             (Except for mild cognitive impairment caused by tumor);&#xD;
&#xD;
          3. Prior malignancy active within the previous 3 years except for locally curable cancers&#xD;
             that have been apparently cured, such as basal or squamous cell skin cancer,&#xD;
             superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast;&#xD;
&#xD;
          4. Patients with stroke within 6 months before the first dose (except for those with&#xD;
             &quot;multiple lacunar infarction&quot; indicated by imaging examination, but no need for&#xD;
             treatment) or with a history of intracranial hemorrhage (except for intracranial&#xD;
             hemorrhage after surgery);&#xD;
&#xD;
          5. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4&#xD;
             antibody, or any other antibody or drug specifically targeting T-cell co-stimulation&#xD;
             or checkpoint pathways;&#xD;
&#xD;
          6. Concurrent medical condition requiring the use of immunosuppressive medications, or&#xD;
             immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses &gt; 10&#xD;
             mg/day prednisone or equivalent are prohibited within 14 days before the first dose;&#xD;
&#xD;
          7. Active infection（needing therapy） or an unexplained fever &gt; 38.5°C during screening or&#xD;
             before the first scheduled day of dosing (subjects with tumor fever may be enrolled at&#xD;
             the discretion of the investigator);&#xD;
&#xD;
          8. Those who received systemic therapy of radiotherapy, chemotherapy, hormone therapy,&#xD;
             surgery, targeted therapy, or antibody drugs within 4 weeks before the first dose;&#xD;
             used monoclonal antibody coupled radionuclide or cytotoxic therapy within 10 weeks&#xD;
             before the first dose; the toxicity of previous anti-tumor therapy has not recovered&#xD;
             to ≤1 (except hair loss);&#xD;
&#xD;
          9. Patients who have a history of organ transplantation or allogeneic bone marrow&#xD;
             transplantation or who have received auto stem cell transplantation or other severe&#xD;
             immune defects within 3 months before the first dose;&#xD;
&#xD;
         10. Patients who are preparing for autologous stem cell transplantation.&#xD;
&#xD;
         11. Patients with active pulmonary tuberculosis;&#xD;
&#xD;
         12. Previous or simultaneous interstitial lung disease (except for interstitial lung&#xD;
             disease caused by radiotherapy and chemotherapy and without symptoms at present);&#xD;
&#xD;
         13. Patients with active hepatitis;&#xD;
&#xD;
         14. Patients with HIV positive;&#xD;
&#xD;
         15. Patients received any other clinical trial drug / device treatment within 4 weeks&#xD;
             before the first administration;&#xD;
&#xD;
         16. Patients with uncontrollable or serious cardiovascular diseases, cardiovascular&#xD;
             diseases such as congestive heart failure, unstable angina pectoris, myocardial&#xD;
             infarction and other cardiovascular diseases of NYHA grade II or above occurred within&#xD;
             6 months before the first dose; uncontrolled hypertension (systolic pressure ≥ 180mmhg&#xD;
             and / or diastolic pressure ≥ 100mmhg);&#xD;
&#xD;
         17. Patients with drug abuse history or alcohol addiction history within 6 months before&#xD;
             the study drug administration;&#xD;
&#xD;
         18. Patients with known previous allergies to macromolecular protein preparations or known&#xD;
             to be allergic to anti-PD-1 / PD-L1 antibodies&#xD;
&#xD;
         19. Patients who received live attenuated vaccine within 4 weeks before the first dose&#xD;
             (except inactivated influenza vaccine such as seasonal influenza vaccine for&#xD;
             injection);&#xD;
&#xD;
         20. Female and male who have reproductive potential must be willing and able to employ a&#xD;
             highly effective method of birth control/contraception to prevent pregnancy while on&#xD;
             treatment and for at least 6 months after receiving the last dose of study treatment.&#xD;
&#xD;
         21. The investigators judged that it was not suitable for the patients to participating in&#xD;
             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>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>October 19, 2020</last_update_submitted>
  <last_update_submitted_qc>October 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 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>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <!-- 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/NCT04457869
org study id: NTP-F520-003
nct id: NCT04457869
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is a multi-center, prospective, open-label, two-stage optimized design, single-arm, phase
      II clinical study to evaluate the efficacy and safety of F520 for the treatment of
      Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL) or Secondary Central
      Nervous System Lymphoma (SCNSL).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: F520
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR) by Independent Review Committee (IRC) Independent Review Committee (IRC).
time frame: Approximately 24 months
description: Response assessment will be performed according to modified IPCG response. criteria on contrastenhanced cranial MRI-scans.
measure: Objective response rate (ORR) based on the investigator assessment.
time frame: Approximately 24 months
description: Response assessment will be performed according to modified IPCG response.
measure: Progression-free survival (PFS)
time frame: Approximately 24 months
description: Based on IRC and the investigator assessments.
measure: Duration of response (DOR)
time frame: Approximately 24 months
description: Based on IRC and the investigator assessments.
measure: Overall survival (OS)
time frame: Approximately 24 months
measure: Safety of F520
time frame: Approximately 24 months
description: AE/SAE will be assessed by CTCAE v5.0
arm group label: Single arm
arm group type: Experimental
intervention type: Drug
intervention name: F520
description: 3mg/kg every 3 weeks
arm group label: Single arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Neoplasm Metastasis