<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/NCT04414969</url>
  </required_header>
  <id_info>
    <org_study_id>HNCH-NKT-2020</org_study_id>
    <nct_id>NCT04414969</nct_id>
  </id_info>
  <brief_title>Anti-PD-1 Antibody Combined With Peg-Asparaginase and Chidamide for the Early Stage of NK/T Cell Lymphoma</brief_title>
  <official_title>Anti-PD-1 Antibody, Peg-Asparaginase, Chidamide Combined With Radiotherapy for the First-line Treatment of Patients With Stage I/II Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (ENKTL): An Open-label, Multicenter, Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hunan Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hunan Cancer Hospital</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>
      This prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody&#xD;
      combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin's&#xD;
      lymphoma and shows extremely poor survival. Several retrospective studies and randomized&#xD;
      prospective phase 2 studies have shown that Peg-aspargase based chemotherapy regimens&#xD;
      achieved a promising efficacy in the first line treatment of ENKTL. However, about one third&#xD;
      of patients will relapse or become refractory after Peg-aspargase-based chemotherapy followed&#xD;
      by radiotherapy, and some patients cannot tolerate the toxicities caused by chemotherapy.&#xD;
      Anti-PD-1/PD-L1 antibodies and Chidamide are active drugs for the treatment of&#xD;
      relapsed/refractory ENKTL. However, there is no prospective study to evaluate the efficacy&#xD;
      and safety of anti-PD-1 antibody combine with Peg-asparaginase and Chidamide in the newly&#xD;
      diagnosed early stage ENKTL. This prospective pilot study to evaluate the efficacy and safety&#xD;
      of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE&#xD;
      and IIE ENKTL.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 26, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 1, 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>An Open-label, multicenter, single group, phase II trial,</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>12 weeks after the initiation of the treatment</time_frame>
    <description>complete remission rate + partial remission rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete remission rate</measure>
    <time_frame>12 weeks after the initiation of the treatment</time_frame>
    <description>complete remission rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to three years after the start of the study</time_frame>
    <description>Time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first, otherwise subject data were censored at time last known disease free.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to three years after the start of the study</time_frame>
    <description>Time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first, and otherwise censored at time last known alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety issue</measure>
    <time_frame>Up to one year after the end of the study</time_frame>
    <description>All the adverse events of the patients related will be assessed and graded by NCI CTCAE v 5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Immune Checkpoint Inhibitor</condition>
  <condition>Chemotherapy Effect</condition>
  <condition>Epigenetic Disorder</condition>
  <condition>NK/T-cell Lymphoma of Nasal Cavity</condition>
  <arm_group>
    <arm_group_label>Anti-PD-1 antibody+Peg-Asparaginase+Chidamide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anti-PD-1 antibody 200mg ivdrip d1; PEG-ASP 2500U/m2 im d1; Chidamide, 30mg, PO, on d1，d5，d8，d12，d15，d19; repeat every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-PD-1 antibody+Peg-Asparaginase+Chidamide</intervention_name>
    <description>Anti-PD-1 antibody 200mg ivdrip d1, PEG-ASP 2500U/m2 im d1, Chidamide, 30mg, po, on d1，d5，d8，d12，d15，d19. The regimen was repeated every 3 weeks for 4 cycles followed by involved-field radiotherapy after got CR and PR (patients with efficacy of SD and PD withdrew from the study). Intensity-modulated radiation treatment was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 54-56 Gy. During the radiotherapy, the anti-PD-1 antibody is administrated (200mg ivdrip, every 3 weeks) for 2 cycles. After the completion of radiotherapy, the subsequent 2 cycles of anti-PD-1 antibody + Peg-Asparaginase + Chidamide are administrated. After the end of all the above induction treatments , anti-PD-1 antibody (200mg ivdrip, every 3 weeks for up to 9 cycles) is given as maintenance therapy for 6 months (the total cycles of anti-PD-1 antibody is 17）.</description>
    <arm_group_label>Anti-PD-1 antibody+Peg-Asparaginase+Chidamide</arm_group_label>
    <other_name>Anti-PD-1 antibody；Peg-Asparaginase；Chidamide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pathologically confirmed, previously untreated ENKTL with stage I/II (for stage I, the&#xD;
             patients should have one or more of the following risk factors: ①Extensive local&#xD;
             invasion and or bone destruction: invasion of the inner orbital wall or bottom wall,&#xD;
             orbital apex, orbital contents, maxillary sinus, sphenoid sinus, frontal sinus or&#xD;
             ethmoid sinus invasion, hard palate, ethmoid plate, nasopharynx, slope bone is&#xD;
             invaded. ②Skin invasion: nose and or cheek skin invasion; ③Waldeyer's ring invasion;&#xD;
             ④LDH&gt;upper limit of normal; ⑤EBV-DNA &gt; upper limit of normal; ⑥B symptoms);&#xD;
&#xD;
          2. Age range from 18 to 75 years;&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;&#xD;
&#xD;
          4. At least one evaluable or measurable lesion complying with Lugano 2014 Standard&#xD;
             (evaluable lesion: the examination show increased uptake of lymph nodes or extranodal&#xD;
             areas (higher than that of the liver) by 18F-Fluorodeoxyglucose/Positron Emission&#xD;
             Tomography (18FDG/PET) and the PET and/or Computed Tomography (CT) features coincide&#xD;
             with lymphoma characteristics; measurable lesion: nodal lesions were longer than 15 mm&#xD;
             or extranodal lesions were longer than 10 mm, and accompanied by increased 18FDG&#xD;
             uptake). Increased liver or spleen diffuse 18FDG uptake without measurable lesions&#xD;
             should be excluded.&#xD;
&#xD;
          5. Adequate haematologic function (haemoglobin ≥90 g/l, absolute neutrophil count ≥&#xD;
             1500/ml, platelets ≥ 80×10e9/l),&#xD;
&#xD;
          6. Adequate hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of&#xD;
             normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper&#xD;
             limit of normal),&#xD;
&#xD;
          7. Hepatitis B virus carriers should have HBV-DNA &lt;10e4 copies and should use antiviral&#xD;
             drugs.&#xD;
&#xD;
          8. Adequate renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50&#xD;
             ml/min);&#xD;
&#xD;
          9. Normal coagulation function and electrocardiogram results.&#xD;
&#xD;
         10. No previous anti-cancer treatment including chemotherapy, radiotherapy, immunotherapy,&#xD;
             biological therapy, glucocorticoids therapy for lymphoma.&#xD;
&#xD;
         11. Willingness to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of other malignancy within the past 5 years (except for basal cell carcinoma&#xD;
             of the skin and carcinoma in situ of the cervix)&#xD;
&#xD;
          2. With clinically diagnosed hemophagocytic syndrome (HPS); or aggressive NK cell&#xD;
             leukemia; or central nervous system invasion;&#xD;
&#xD;
          3. Previous treatments with immune checkpoint inhibitor, including nivolumab,&#xD;
             pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, sintilimab, etc.&#xD;
&#xD;
          4. Previous treatments with HDAC inhibitor, including Chidamide, romidepsin,&#xD;
             panobinostat, belinostat, etc.&#xD;
&#xD;
          5. Patients allergic of any of drug in this regimen;&#xD;
&#xD;
          6. Pregnant or lactating women&#xD;
&#xD;
          7. Participated in other clinical trials within the 4 weeks prior to enrollment;&#xD;
&#xD;
          8. History of severe hemorrhage, or any bleeding events with a severe grade of 3 or more&#xD;
             in CTCAE 5.0 within 4 weeks prior to enrollment&#xD;
&#xD;
          9. Blood pressure unable to be controlled ideally with single antihypertensive drug&#xD;
             therapy (Systolic blood pressure &gt; 140 mmHg, Diastolic Blood Pressure &gt; 90 mmHg);&#xD;
             Clinically significant cardiovascular disease (e.g. activity) including history of CVA&#xD;
             (within 6 months), myocardial infarction (within 6 months), unstable angina, New York&#xD;
             Heart Association (NYHA) Grade II or greater congestive heart failure; serious cardiac&#xD;
             arrhythmia beyond drug control or potentially affecting experimental therapy.&#xD;
&#xD;
         10. The subject is being treated with immunosuppressive agents, glucocorticoids （systemic&#xD;
             or absorbable local using）for immunosuppression purposes (dose&gt; 10 mg / day prednisone&#xD;
             or other therapeutic glucocorticoids) within two weeks before enrollment the study.&#xD;
&#xD;
         11. Abnormal coagulation or bleeding tendency (It must be satisfied that INR is under&#xD;
             normal range without anticoagulant within 14 days prior to signing informed consent);&#xD;
             patients treated with anticoagulants or vitamin K antagonists such as warfarin,&#xD;
             heparin or their analogues; on the premise that the international standardized ratio&#xD;
             of prothrombin time (INR) is less than 1.5, small doses of warfarin (1 mg po, qd) or&#xD;
             aspirin (no more than 100 mg qd) are allowed for preventive purposes.&#xD;
&#xD;
         12. Arterial or venous thromboembolic events occurred within 6 months, such as&#xD;
             cerebrovascular accident (including transient ischemic attack), deep vein thrombosis&#xD;
             (venous thrombosis caused by intravenous catheterization due to precancerous&#xD;
             chemotherapy is excluded if it has been cured judged by the researchers) and pulmonary&#xD;
             embolism.&#xD;
&#xD;
         13. Suffered major surgery within 42 days prior to enrollment;&#xD;
&#xD;
         14. Have an active autoimmune disease that requires systemic treatment within the past two&#xD;
             years.&#xD;
&#xD;
         15. Severe or uncontrolled infections, except fever associated with lymphoma B symptoms.&#xD;
&#xD;
         16. History of psychotropic drug abuse and unable to get rid of or with mental disorders;&#xD;
&#xD;
         17. History of immunodeficiency, including HIV positive testing, or other acquired,&#xD;
             congenital immunodeficiency disorders, or organ transplantation history;&#xD;
&#xD;
         18. Patients with concomitant diseases which could seriously endanger their own safety or&#xD;
             could affect completion of the study according to investigators' judgment.&#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>Hui Zhou, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Lymphoma and Hematology, Hunan Cancer Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hui Zhou, M.D.</last_name>
    <phone>86-0731-89762281</phone>
    <email>zhouhui@hnca.org.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ya-Jun Li, M.D.</last_name>
    <phone>86-0731-89762281</phone>
    <email>liyajun@hnca.org.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hunan Cancer Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410013</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hui Zhou, MD.</last_name>
      <phone>8673189762281</phone>
      <email>Zhouhui@hnca.org.cn</email>
    </contact>
    <contact_backup>
      <last_name>Yajun Li, MD.</last_name>
      <phone>8673189762281</phone>
      <email>liyajun@hnca.org.cn</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 31, 2020</study_first_submitted>
  <study_first_submitted_qc>May 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hunan Cancer Hospital</investigator_affiliation>
    <investigator_full_name>Ya-Jun Li</investigator_full_name>
    <investigator_title>Sub-Investigator</investigator_title>
  </responsible_party>
  <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>Asparaginase</mesh_term>
    <mesh_term>Pegaspargase</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</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/NCT04414969
org study id: HNCH-NKT-2020
nct id: NCT04414969
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody
      combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL.
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin's
      lymphoma and shows extremely poor survival. Several retrospective studies and randomized
      prospective phase 2 studies have shown that Peg-aspargase based chemotherapy regimens
      achieved a promising efficacy in the first line treatment of ENKTL. However, about one third
      of patients will relapse or become refractory after Peg-aspargase-based chemotherapy followed
      by radiotherapy, and some patients cannot tolerate the toxicities caused by chemotherapy.
      Anti-PD-1/PD-L1 antibodies and Chidamide are active drugs for the treatment of
      relapsed/refractory ENKTL. However, there is no prospective study to evaluate the efficacy
      and safety of anti-PD-1 antibody combine with Peg-asparaginase and Chidamide in the newly
      diagnosed early stage ENKTL. This prospective pilot study to evaluate the efficacy and safety
      of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE
      and IIE ENKTL.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: An Open-label, multicenter, single group, phase II trial,
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: 12 weeks after the initiation of the treatment
description: complete remission rate + partial remission rate
measure: Complete remission rate
time frame: 12 weeks after the initiation of the treatment
description: complete remission rate
measure: Progression Free Survival (PFS)
time frame: Up to three years after the start of the study
description: Time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first, otherwise subject data were censored at time last known disease free.
measure: Overall Survival (OS)
time frame: Up to three years after the start of the study
description: Time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first, and otherwise censored at time last known alive.
measure: Safety issue
time frame: Up to one year after the end of the study
description: All the adverse events of the patients related will be assessed and graded by NCI CTCAE v 5.0
arm group label: Anti-PD-1 antibody+Peg-Asparaginase+Chidamide
arm group type: Experimental
description: Anti-PD-1 antibody 200mg ivdrip d1; PEG-ASP 2500U/m2 im d1; Chidamide, 30mg, PO, on d1，d5，d8，d12，d15，d19; repeat every 3 weeks.
intervention type: Drug
intervention name: Anti-PD-1 antibody+Peg-Asparaginase+Chidamide
description: Anti-PD-1 antibody 200mg ivdrip d1, PEG-ASP 2500U/m2 im d1, Chidamide, 30mg, po, on d1，d5，d8，d12，d15，d19. The regimen was repeated every 3 weeks for 4 cycles followed by involved-field radiotherapy after got CR and PR (patients with efficacy of SD and PD withdrew from the study). Intensity-modulated radiation treatment was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 54-56 Gy. During the radiotherapy, the anti-PD-1 antibody is administrated (200mg ivdrip, every 3 weeks) for 2 cycles. After the completion of radiotherapy, the subsequent 2 cycles of anti-PD-1 antibody + Peg-Asparaginase + Chidamide are administrated. After the end of all the above induction treatments , anti-PD-1 antibody (200mg ivdrip, every 3 weeks for up to 9 cycles) is given as maintenance therapy for 6 months (the total cycles of anti-PD-1 antibody is 17）.
arm group label: Anti-PD-1 antibody+Peg-Asparaginase+Chidamide
other name: Anti-PD-1 antibody；Peg-Asparaginase；Chidamide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hui Zhou, M.D.
role: Principal Investigator
affiliation: Department of Lymphoma and Hematology, Hunan Cancer Hospital
last name: Hui Zhou, M.D.
phone: 86-0731-89762281
email: zhouhui@hnca.org.cn
last name: Ya-Jun Li, M.D.
phone: 86-0731-89762281
email: liyajun@hnca.org.cn
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Hunan Cancer Hospital
investigator full name: Ya-Jun Li
investigator title: Sub-Investigator
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Asparaginase
mesh term: Pegaspargase
mesh term: Antibodies
mesh term: Immunoglobulins
sharing ipd: No