<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/NCT02987244</url>
  </required_header>
  <id_info>
    <org_study_id>PUMCH-NHL-002</org_study_id>
    <nct_id>NCT02987244</nct_id>
  </id_info>
  <brief_title>Chidamide Plus CHOEP Combined With Upfront ASCT in Untreated Peripheral T-cell Lymphoma</brief_title>
  <official_title>Chidamide Plus CHOEP Combined With Upfront ASCT in Untreated Peripheral T-cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University First Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University Third Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University Cancer Hospital &amp; Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tianjin Medical University Cancer Institute and Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine determine the maximum tolerated dose (MTD) and&#xD;
      safety of the combination of Chidamide combined with CHOEP(cyclophosphamide，&#xD;
      epirubicin,vindesine, etoposide and prednisone) regimen as first line treatment in&#xD;
      newly-diagnosed T-NHL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chidamide+Cyclophosphamide+Epirubicin+Vindesine+Etoposide+Prednisone Six cycles of therapy&#xD;
      administered every 28 days were planned. Cyclophosphamide 750mg/m2 IV d1; epirubicin 70mg/m2&#xD;
      IV d1; Vindesine 4mg IV d1; etoposide 100mg IV d1-3; prednisone 60mg/m2 PO d1-5.&#xD;
&#xD;
      Chidamide:&#xD;
&#xD;
      Phase I: Patients were treated at the following bortezomib dose levels: 15, 20, and 25 mg&#xD;
      twice per week.&#xD;
&#xD;
      Dose escalation and reduction were on the basis of the continual reassessment method, with at&#xD;
      least two patients per dose level and no dose level skipped. No intrapatient dose escalation&#xD;
      will be allowed. If one patient experienced dose-limiting toxicity (DLT), three additional&#xD;
      patients were added to the dose level. If two of six patients experienced DLT, the previous&#xD;
      dose level was declared the MTD. If only one of six patients experienced DLT, dose escalation&#xD;
      was permitted to continue. DLT refers only to toxic events that occur during the first cycle&#xD;
      of treatment.&#xD;
&#xD;
      At least 9(3+3+3) patients will be enrolled in Phase I study. Phase II: If MTD was not&#xD;
      reached at 25mg dose level of Chidamide. The followed study will use 20mg twice per week as&#xD;
      experimental dose.&#xD;
&#xD;
      After 3 Cycles, patients who become PD should withdraw the trial and receive other regimens;&#xD;
      patients who become CR and eligible for auto-SCT will undergo auto-SCT; patients who get PR&#xD;
      will receive 3 more cycles C-CHOEP regimen treatment, CR patients in them undergo auto-SCT,&#xD;
      non-CR patients undergo follow-up phase.&#xD;
&#xD;
      All the patients will continue to receive chidamide treatment until progression of the&#xD;
      disease (PD), unacceptable toxicity, or patient/investigator discretion.&#xD;
&#xD;
      During follow-uo phase, surveillance imaging with CT scans can be performed every 6 months up&#xD;
      to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease&#xD;
      relapses.&#xD;
&#xD;
      from recruiting the first subject until the last recruited subject finished his 2 years&#xD;
      follow-up phase or the disease relapsed&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>March 2016</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2 years progression-free survival</measure>
    <time_frame>the overall time frame is up to 48 months</time_frame>
    <description>from recruiting the first subject until the last recruited subject finished his 2 years follow-up phase or the disease relapsed</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>5 years overall survival（OS）</measure>
    <time_frame>the overall time frame is up to 84 months</time_frame>
    <description>from recruiting the first subject until the last recruited subject finished his 5 years follow-up phase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall response rate(ORR) and complete remission rate(CR）</measure>
    <time_frame>the overall time frame is up to 30 months</time_frame>
    <description>the last recruited subject finished 4 cycle C-CHOEP regimen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>the overall time frame is up to 84 months</time_frame>
    <description>throughout the treatment and until 30 days after the administration of the last dose of a study drug</description>
  </secondary_outcome>
  <other_outcome>
    <measure>maximum tolerated dose of chidamide</measure>
    <time_frame>the overall time frame is up to 6 months</time_frame>
    <description>from recruiting the first 9 subjects to all of them received 1 cycle C-CHOEP regiment</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>T Cell Non-Hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>C-CHOEP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>experimental arm will be treated by Chidamide combined CHOEP ( cyclophosphamide, epirubicine, vindesine, etoposide and prednisone) regimen for 6 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chidamide</intervention_name>
    <description>Six cycles of therapy will be administered,and each cycle of treatment is 28 days.&#xD;
Phase I: Patients were treated at the following dose levels: 15, 20, and 25 mg twice per week to determine the MDT Phase II: If MTD was not reached at 25mg dose level of Chidamide. The followed study will use 20mg twice per week as experimental dose.</description>
    <arm_group_label>C-CHOEP</arm_group_label>
    <other_name>epidaza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide(750mg/m2) was administered intravenously on d1</description>
    <arm_group_label>C-CHOEP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epirubicin</intervention_name>
    <description>epirubicin (70mg/m2)was administered intravenously on d1;</description>
    <arm_group_label>C-CHOEP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vindesine</intervention_name>
    <description>vindesine (4mg)was administered intravenously on d1;</description>
    <arm_group_label>C-CHOEP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>etoposide (100mg) was administered intravenously on d1,2,3.</description>
    <arm_group_label>C-CHOEP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>prednisone (60mg/m2)was administered intravenously by oral d1-5.</description>
    <arm_group_label>C-CHOEP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly-diagnosed T cell non-Hodgkin's lymphoma patients. Diagnosis of T cell NHL was&#xD;
             performed by morphologic analysis of tissue pathological specimens along with&#xD;
             Immunohistochemistry (IHC)&#xD;
&#xD;
          -  ECOG≤2&#xD;
&#xD;
          -  At least one or more unidimensionally measurable lesions (≥1 cm by CT scan or skin&#xD;
             lesions or a measurable lesion by physical examination)&#xD;
&#xD;
          -  Sign the Informed consent&#xD;
&#xD;
          -  Women of childbearing potential must understand that the study medication could have a&#xD;
             potential teratogenic risk. They should undergo complete contraception during the&#xD;
             study period.&#xD;
&#xD;
          -  Male subjects must agree to use condoms throughout study drug therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  T lymphoblastic leukemia/lymphoma&#xD;
&#xD;
          -  Bone marrow involvement and lymphoma cell ≥ 25%&#xD;
&#xD;
          -  Aplastic large T cell lymphoma - ALK positive&#xD;
&#xD;
          -  NK/T-cell lymphoma&#xD;
&#xD;
          -  Mycosis Fungoides/Sezary Syndrome&#xD;
&#xD;
          -  Pre-existing uncontrolled active infection&#xD;
&#xD;
          -  Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart&#xD;
             Association criteria&#xD;
&#xD;
          -  Grade 3 or 4 peripheral neuropathy&#xD;
&#xD;
          -  Pregnancy or active lactation&#xD;
&#xD;
          -  Co-existing tumors&#xD;
&#xD;
          -  Impaired renal/ hepatic function (serum creatinine &gt;1.5 mg/dl or creatinine clearance&#xD;
             &lt;60 ml/min or serum transaminases/ bilirubin ≥3 upper limits of normal）&#xD;
&#xD;
          -  History of mental illness&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daobin Zhou, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei Zhang, M.D</last_name>
    <phone>+86 136 8147 3557</phone>
    <email>vv1223@vip.sina.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yan Zhang, M.D</last_name>
    <phone>+86 13810000485</phone>
    <email>zhangyan10659@pumch.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peking Union medical college hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wei Zhang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Tianjin medical universty cancer institute &amp; hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Dong M, Ning ZQ, Xing PY, Xu JL, Cao HX, Dou GF, Meng ZY, Shi YK, Lu XP, Feng FY. Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas. Cancer Chemother Pharmacol. 2012 Jun;69(6):1413-22. doi: 10.1007/s00280-012-1847-5. Epub 2012 Feb 24.</citation>
    <PMID>22362161</PMID>
  </reference>
  <reference>
    <citation>Shi Y, Dong M, Hong X, Zhang W, Feng J, Zhu J, Yu L, Ke X, Huang H, Shen Z, Fan Y, Li W, Zhao X, Qi J, Huang H, Zhou D, Ning Z, Lu X. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015 Aug;26(8):1766-71. doi: 10.1093/annonc/mdv237. Epub 2015 Jun 23.</citation>
    <PMID>26105599</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 6, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <last_update_submitted>December 6, 2016</last_update_submitted>
  <last_update_submitted_qc>December 6, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 8, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chidamide, T Cell Non-Hodgkin's Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</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>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Epirubicin</mesh_term>
    <mesh_term>Vindesine</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/NCT02987244
org study id: PUMCH-NHL-002
nct id: NCT02987244
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to determine determine the maximum tolerated dose (MTD) and
      safety of the combination of Chidamide combined with CHOEP(cyclophosphamide，
      epirubicin,vindesine, etoposide and prednisone) regimen as first line treatment in
      newly-diagnosed T-NHL.
Chidamide+Cyclophosphamide+Epirubicin+Vindesine+Etoposide+Prednisone Six cycles of therapy
      administered every 28 days were planned. Cyclophosphamide 750mg/m2 IV d1; epirubicin 70mg/m2
      IV d1; Vindesine 4mg IV d1; etoposide 100mg IV d1-3; prednisone 60mg/m2 PO d1-5.

      Chidamide:

      Phase I: Patients were treated at the following bortezomib dose levels: 15, 20, and 25 mg
      twice per week.

      Dose escalation and reduction were on the basis of the continual reassessment method, with at
      least two patients per dose level and no dose level skipped. No intrapatient dose escalation
      will be allowed. If one patient experienced dose-limiting toxicity (DLT), three additional
      patients were added to the dose level. If two of six patients experienced DLT, the previous
      dose level was declared the MTD. If only one of six patients experienced DLT, dose escalation
      was permitted to continue. DLT refers only to toxic events that occur during the first cycle
      of treatment.

      At least 9(3+3+3) patients will be enrolled in Phase I study. Phase II: If MTD was not
      reached at 25mg dose level of Chidamide. The followed study will use 20mg twice per week as
      experimental dose.

      After 3 Cycles, patients who become PD should withdraw the trial and receive other regimens;
      patients who become CR and eligible for auto-SCT will undergo auto-SCT; patients who get PR
      will receive 3 more cycles C-CHOEP regimen treatment, CR patients in them undergo auto-SCT,
      non-CR patients undergo follow-up phase.

      All the patients will continue to receive chidamide treatment until progression of the
      disease (PD), unacceptable toxicity, or patient/investigator discretion.

      During follow-uo phase, surveillance imaging with CT scans can be performed every 6 months up
      to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease
      relapses.

      from recruiting the first subject until the last recruited subject finished his 2 years
      follow-up phase or the disease relapsed
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 2 years progression-free survival
time frame: the overall time frame is up to 48 months
description: from recruiting the first subject until the last recruited subject finished his 2 years follow-up phase or the disease relapsed
measure: 5 years overall survival（OS）
time frame: the overall time frame is up to 84 months
description: from recruiting the first subject until the last recruited subject finished his 5 years follow-up phase
measure: overall response rate(ORR) and complete remission rate(CR）
time frame: the overall time frame is up to 30 months
description: the last recruited subject finished 4 cycle C-CHOEP regimen
measure: adverse events
time frame: the overall time frame is up to 84 months
description: throughout the treatment and until 30 days after the administration of the last dose of a study drug
measure: maximum tolerated dose of chidamide
time frame: the overall time frame is up to 6 months
description: from recruiting the first 9 subjects to all of them received 1 cycle C-CHOEP regiment
arm group label: C-CHOEP
arm group type: Experimental
description: experimental arm will be treated by Chidamide combined CHOEP ( cyclophosphamide, epirubicine, vindesine, etoposide and prednisone) regimen for 6 cycles.
intervention type: Drug
intervention name: Chidamide
description: Six cycles of therapy will be administered,and each cycle of treatment is 28 days.
Phase I: Patients were treated at the following dose levels: 15, 20, and 25 mg twice per week to determine the MDT Phase II: If MTD was not reached at 25mg dose level of Chidamide. The followed study will use 20mg twice per week as experimental dose.
arm group label: C-CHOEP
other name: epidaza
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide(750mg/m2) was administered intravenously on d1
arm group label: C-CHOEP
intervention type: Drug
intervention name: Epirubicin
description: epirubicin (70mg/m2)was administered intravenously on d1;
arm group label: C-CHOEP
intervention type: Drug
intervention name: Vindesine
description: vindesine (4mg)was administered intravenously on d1;
arm group label: C-CHOEP
intervention type: Drug
intervention name: Etoposide
description: etoposide (100mg) was administered intravenously on d1,2,3.
arm group label: C-CHOEP
intervention type: Drug
intervention name: Prednisone
description: prednisone (60mg/m2)was administered intravenously by oral d1-5.
arm group label: C-CHOEP
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Daobin Zhou, M.D
role: Principal Investigator
affiliation: Peking Union Medical College Hospital
last name: Wei Zhang, M.D
phone: +86 136 8147 3557
email: vv1223@vip.sina.com
last name: Yan Zhang, M.D
phone: +86 13810000485
email: zhangyan10659@pumch.cn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
country: China
citation: Dong M, Ning ZQ, Xing PY, Xu JL, Cao HX, Dou GF, Meng ZY, Shi YK, Lu XP, Feng FY. Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas. Cancer Chemother Pharmacol. 2012 Jun;69(6):1413-22. doi: 10.1007/s00280-012-1847-5. Epub 2012 Feb 24.
PMID: 22362161
citation: Shi Y, Dong M, Hong X, Zhang W, Feng J, Zhu J, Yu L, Ke X, Huang H, Shen Z, Fan Y, Li W, Zhao X, Qi J, Huang H, Zhou D, Ning Z, Lu X. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015 Aug;26(8):1766-71. doi: 10.1093/annonc/mdv237. Epub 2015 Jun 23.
PMID: 26105599
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Etoposide
mesh term: Epirubicin
mesh term: Vindesine
sharing ipd: No