<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/NCT03023358</url>
  </required_header>
  <id_info>
    <org_study_id>CDOP201602</org_study_id>
    <nct_id>NCT03023358</nct_id>
  </id_info>
  <brief_title>Compared the Efficacy and Safety of CDOP Combined With Chidamide and CDOP in de Novo Peripheral T Cell Lymphoma Patients</brief_title>
  <official_title>Compared the Efficacy and Safety of CDOP Combined With Chidamide and CDOP in de Novo Peripheral T Cell Lymphoma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanfang Hospital, Southern Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prognosis for Peripheral T cell lymphomas (PTCL) remains poor in comparison to B cell&#xD;
      NHL. This is largely due to lower response rates and less durable responses to standard&#xD;
      combination chemotherapy regimens such as CHOP. Whether CDOP plus Chidamide can improve the&#xD;
      prognosis for PTCL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphoproliferative disorder&#xD;
      arising from mature T-cells of post-thymic origin. PTCL represent a relatively uncommon group&#xD;
      of hematologic malignancies within non-Hodgkin lymphomas (NHL), accounting for about 10% of&#xD;
      NHL cases. The prognosis for PTCL remains poor in comparison to B-cell NHL. This is largely&#xD;
      due to lower response rates and less durable responses to standard combination chemotherapy&#xD;
      regimens such as CHOP. Progress has been further hampered by the relative rarity and the&#xD;
      biological heterogeneity of the diseases. Among PTCL cases worldwide, the most common&#xD;
      subtypes include PTCL-not otherwise specified (PTCL-NOS; 26%), angioimmunoblastic T-cell&#xD;
      lymphoma (AITL; 18.5%), NK/T-cell lymphoma (10%), adult T-cell leukemia/lymphoma (ATLL; 10%),&#xD;
      ALK-positive anaplastic large cell lymphoma (ALCL; 7%) and ALK-negative ALCL (6%); subtypes&#xD;
      such as enteropathy-associated T-cell lymphoma (EATL; &lt;5%) and primary cutaneous ALCL are&#xD;
      relatively rare (&lt;2%) with ALCL more common than NK/T or ATLL in the United States.&#xD;
&#xD;
      PTCLs are less responsive to and have less frequent durable remissions with standard&#xD;
      chemotherapy regimens such as CHOP and thus carry a poorer prognosis compared to diffuse&#xD;
      large B-cell lymphomas. In prospective randomized studies, PTCLs have been included with&#xD;
      aggressive B-cell lymphomas. However, it has not been possible to assess the impact of&#xD;
      chemotherapy in this subgroup of patients with PTCLs due to small sample size. Only limited&#xD;
      data exist from randomized trials comparing the efficacy of chemotherapy regimens exclusively&#xD;
      in patients with PTCL.&#xD;
&#xD;
      CHOP chemotherapy is the most commonly used first-line regimen for patients with PTCL.&#xD;
      However, with the exception of ALK+ ALCL, outcomes are disappointing compared to the&#xD;
      favorable results achieved with DLBCL. Chemotherapy regimens that are more intensive than&#xD;
      CHOP have not shown any significant improvement in OS in patients with PTCL, with the&#xD;
      exception of ALCL.&#xD;
&#xD;
      CHOP chemotherapy is frequently curative in only the small number of patients with favorable&#xD;
      prognostic features. As previously discussed, retrospective analysis from the International&#xD;
      T-cell Lymphoma Project showed that anthracycline-based chemotherapy did not favorably impact&#xD;
      survival in patients with the most common forms of PTCLs, namely PTCL-NOS and AITL. In a&#xD;
      retrospective study conducted by the British Columbia cancer agency, the 5-year OS rate for&#xD;
      patients with PTCL-NOS primarily treated with CHOP or CHOP-like regimens was only 35%; among&#xD;
      these patients, the 5-year OS rates were higher in patients with low-risk IPI scores compared&#xD;
      with those with high-risk IPI scores (64% vs. 22%, respectively). In addition, patients with&#xD;
      ALK-positive ALCL had superior clinical outcome compared to those with ALK-negative ALCL&#xD;
      (5-year OS 58% vs. 34%, respectively). The addition of etoposide to CHOP (CHOEP regimen)&#xD;
      compared with CHOP alone was evaluated in a randomized study by the German High-grade NHL&#xD;
      Study Group (DSHNHL). In relatively young patients with favorable prognosis aggressive NHL&#xD;
      (age ≤60 years; normal LDH levels), the CHOEP regimen resulted in significantly higher CR&#xD;
      rate (88% vs. 79%; P=0.003) and 5-year EFS rate (69% vs. 58%; P=0.004). No difference was&#xD;
      observed in OS outcomes between the regimens. It should also be noted that in this study, the&#xD;
      majority of patients had B-cell histology, with only 14% diagnosed with T-cell NHL (with 12%&#xD;
      of patients having ALCL, PTCL-NOS, or AITL histology).36 In an analysis of a large cohort of&#xD;
      patients with PTCL treated within the DSHNHL trials, patients with ALK- positive ALCL had&#xD;
      favorable outcomes with CHOP or CHOP with etoposide (CHOEP). Three-year EFS and OS rates were&#xD;
      76% and 90%, respectively, for patients with ALK-positive ALCL. The corresponding outcomes&#xD;
      were 50% and 67.5%, respectively, for AITL, 46% and 62%, respectively, for ALK-negative ALCL&#xD;
      and 41% and 54%, respectively, for PTCL-NOS. Among those with T-cell lymphoma, CHOEP was&#xD;
      associated with a trend for improved EFS among relatively young patients (age &lt;60 years) and&#xD;
      is an option for these patients. CHOP-21 appeared to be the standard regimen for patients age&#xD;
      &gt;60 years, given that the addition of etoposide did not provide an advantage in these older&#xD;
      patients due to increased toxicity. Among patients with ALK-negative ALCL, AITL and PTCL-NOS,&#xD;
      those with low-risk IPI scores (IPI &lt;1) had a relatively favorable prognosis; contrastingly,&#xD;
      patients with higher risk IPI scores derived minimal benefit from CHOP or CHOEP.&#xD;
&#xD;
      Histone deacetylases (HDACs) are involved in the remodeling of chromatin and play a key role&#xD;
      in the epigenetic regulation of gene expression. HDACs act as transcription repressors by&#xD;
      removing acetyl groups from the e-amino- terminus of lysine residues within histones to&#xD;
      promote tighter winding of DNA around histone proteins. Elevated expression or activity of&#xD;
      HDACs is implicated in the development and progression of cancer. Inhibition of HDAC enzymes&#xD;
      results in increased histone acetylation, thereby inducing an open chromatin conformation and&#xD;
      transcription of previously dormant genes. At least 18 human HDACs have been identified and&#xD;
      are grouped into four classes. HDAC enzymes class I (HDAC1, 2, 3, and 8), class II (HDAC4, 5,&#xD;
      7, and 9 as IIa, and HDAC6 and 10 as IIb), and class IV (HDAC11) utilize a zinc-catalyzed&#xD;
      mechanism for deacetylation of histones and non-histone proteins, whereas class III (SIRT&#xD;
      1-7) HDACs are NAD+ dependent deacetylase enzymes. Although the precise biological functions&#xD;
      of individual HDACs are still largely unknown, the importance of HDAC enzymes in the&#xD;
      malignant phenotype has been most closely associated with Class I HDACs 1-3. In addition,&#xD;
      Class IIb HDACs 6 and 10 have been found to play a role in the expression and stability of&#xD;
      tumor angiogenesis gene products.&#xD;
&#xD;
      The synthesis of small-molecule HDAC inhibitors (HDACi) has been an active focus in the field&#xD;
      of anticancer drug discovery in recent years. Several different chemical classes of HDACi&#xD;
      have been described, including hydroxamic acids, carboxylic or short-chain fatty acids,&#xD;
      cyclic peptides, and benzamides. Examples of each of these classes have entered clinical&#xD;
      development as antitumor agents. Among them, the hydroxamic acid vorinostat (SAHA) and cyclic&#xD;
      peptide romidepsin (FK-228) were approved in the United States for the treatment of cutaneous&#xD;
      T-cell lymphoma, and very recently, romidepsin for peripheral T-cell lymphoma.&#xD;
&#xD;
      chidamide (CS055/HBI-8000), a new member of the benzamide class of HDACi. Chidamide inhibits&#xD;
      HDAC1, 2, 3, and 10 in the low nanomolar concentration range with broad spectrum antitumor&#xD;
      activity in vitro and in vivo. Mechanism studies have demonstrated that chidamide stimulates&#xD;
      human immune cell-mediated tumor cell killing activity with increased expression of genes and&#xD;
      proteins involved in natural killer (NK) cell functions.&#xD;
&#xD;
      Chidamide was found to be a low nanomolar inhibitor of HDAC1, 2, 3, and 10, the HDAC isotypes&#xD;
      well documented to be associated with the malignant phenotype. Significant and broad spectrum&#xD;
      in vitro and in vivo anti- tumor activity, including a wide therapeutic index, was observed.&#xD;
      Chidamide was also shown to enhance the cytotoxic effect of human peripheral mononuclear&#xD;
      cells ex vivo on K562 target cells, accompanied by the upregulation of proteins involved in&#xD;
      NK cell functions. Furthermore, the expression of a number of genes involved in immune cell-&#xD;
      mediated antitumor activity was observed to be upregulated in peripheral white blood cells&#xD;
      from two T-cell lymphoma patients who responded to chidamide administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>February 2017</start_date>
  <completion_date type="Anticipated">March 2019</completion_date>
  <primary_completion_date type="Anticipated">March 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>complete remission rate</measure>
    <time_frame>3 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>disease free survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to progression</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">174</enrollment>
  <condition>Peripheral T Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>chidamide regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients receive chidamide (30mg twice every week) po, cyclophosphamide (750mg/m2) iv on day 1, liposomal doxorubicin (30mg/m2) iv on day 1, vincristine (1.4mg/m2, max to 2mg) iv on day 1 and prednisone (100mg/d) po on day 1-5.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CDOP regimen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients receive cyclophosphamide (750mg/m2) iv on day 1, liposomal doxorubicin (30mg/m2) iv on day 1, vincristine (1.4mg/m2, max to 2mg) iv on day 1 and prednisone (100mg/d) po on day 1-5.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>chidamide</intervention_name>
    <description>30mg po twice a week</description>
    <arm_group_label>chidamide regimen</arm_group_label>
    <other_name>epidaza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cyclophosphamide</intervention_name>
    <description>750mg/m2 iv on day 1</description>
    <arm_group_label>CDOP regimen</arm_group_label>
    <arm_group_label>chidamide regimen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>liposomal doxorubicin</intervention_name>
    <description>30mg/m2 iv on day 1</description>
    <arm_group_label>CDOP regimen</arm_group_label>
    <arm_group_label>chidamide regimen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vincristine</intervention_name>
    <description>1.4mg/m2 iv on day 1</description>
    <arm_group_label>CDOP regimen</arm_group_label>
    <arm_group_label>chidamide regimen</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prednisone</intervention_name>
    <description>100mg/d po on day 1-5</description>
    <arm_group_label>CDOP regimen</arm_group_label>
    <arm_group_label>chidamide regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged over 18 years are eligible.&#xD;
&#xD;
          -  Patients must be diagnosed of de love peripheral T cell lymphoma (include PTCL not&#xD;
             otherwise specified, angioimmunoblastic T cell lymphoma, ALK negative anapestic large&#xD;
             cell lymphoma and enteropathy-associated T cell lymphoma). Patients must be&#xD;
             chemo-naive.&#xD;
&#xD;
          -  ECOG PS of 0, 1, 2 at screening.&#xD;
&#xD;
          -  Serum biochemical values with the following limit: - creatine &lt;/= 2.0 mg/dl, - total&#xD;
             bilirubin &lt;/= 2.0mg/dl, - transaminases (SG PT) &lt;/= 3X ULN&#xD;
&#xD;
          -  Ability to understand an provide signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of active systemic infection.&#xD;
&#xD;
          -  Any coexisting medical condition that in the judgment of the treating physician is&#xD;
             likely to interfere with study procedures or results.&#xD;
&#xD;
          -  Nursing women, women of childbearing potential with positive urine pregnancy test, or&#xD;
             women of childbearing potential who are not willing to maintain adequate contraception&#xD;
             (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner)&#xD;
             over the entire course of the study.&#xD;
&#xD;
          -  Patients whom the investigators considered were not applicable.&#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_official>
    <last_name>Ru Feng, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Hematology Nanfang Hospital, The Southern Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ru Feng, M.D.</last_name>
    <phone>+86 13725119762</phone>
    <phone_ext>510515</phone_ext>
    <email>ruth1626@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Qi Wei, M.D.</last_name>
    <phone>+86 13427564102</phone>
    <phone_ext>510515</phone_ext>
    <email>sinbad37@126.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ru Feng</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Ru Feng, M.D.</last_name>
      <phone>+86 13725119762</phone>
      <email>ruth1626@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Qi Wei, M.D.</last_name>
      <phone>+86 13427564102</phone>
      <email>sinbad37@126.com</email>
    </contact_backup>
    <investigator>
      <last_name>Ru Feng, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>http://www.nfyy.com/</url>
    <description>Nan fang Hospital, the Southern Medical University</description>
  </link>
  <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>January 2017</verification_date>
  <study_first_submitted>November 3, 2016</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>January 13, 2017</last_update_submitted>
  <last_update_submitted_qc>January 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nanfang Hospital, Southern Medical University</investigator_affiliation>
    <investigator_full_name>Ru Feng</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>peripheral T cell lymphoma</keyword>
  <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>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Vincristine</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/NCT03023358
org study id: CDOP201602
nct id: NCT03023358
lead sponsor: 
has dmc: Yes
The prognosis for Peripheral T cell lymphomas (PTCL) remains poor in comparison to B cell
      NHL. This is largely due to lower response rates and less durable responses to standard
      combination chemotherapy regimens such as CHOP. Whether CDOP plus Chidamide can improve the
      prognosis for PTCL.
Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphoproliferative disorder
      arising from mature T-cells of post-thymic origin. PTCL represent a relatively uncommon group
      of hematologic malignancies within non-Hodgkin lymphomas (NHL), accounting for about 10% of
      NHL cases. The prognosis for PTCL remains poor in comparison to B-cell NHL. This is largely
      due to lower response rates and less durable responses to standard combination chemotherapy
      regimens such as CHOP. Progress has been further hampered by the relative rarity and the
      biological heterogeneity of the diseases. Among PTCL cases worldwide, the most common
      subtypes include PTCL-not otherwise specified (PTCL-NOS; 26%), angioimmunoblastic T-cell
      lymphoma (AITL; 18.5%), NK/T-cell lymphoma (10%), adult T-cell leukemia/lymphoma (ATLL; 10%),
      ALK-positive anaplastic large cell lymphoma (ALCL; 7%) and ALK-negative ALCL (6%); subtypes
      such as enteropathy-associated T-cell lymphoma (EATL; <5%) and primary cutaneous ALCL are
      relatively rare (<2%) with ALCL more common than NK/T or ATLL in the United States.

      PTCLs are less responsive to and have less frequent durable remissions with standard
      chemotherapy regimens such as CHOP and thus carry a poorer prognosis compared to diffuse
      large B-cell lymphomas. In prospective randomized studies, PTCLs have been included with
      aggressive B-cell lymphomas. However, it has not been possible to assess the impact of
      chemotherapy in this subgroup of patients with PTCLs due to small sample size. Only limited
      data exist from randomized trials comparing the efficacy of chemotherapy regimens exclusively
      in patients with PTCL.

      CHOP chemotherapy is the most commonly used first-line regimen for patients with PTCL.
      However, with the exception of ALK+ ALCL, outcomes are disappointing compared to the
      favorable results achieved with DLBCL. Chemotherapy regimens that are more intensive than
      CHOP have not shown any significant improvement in OS in patients with PTCL, with the
      exception of ALCL.

      CHOP chemotherapy is frequently curative in only the small number of patients with favorable
      prognostic features. As previously discussed, retrospective analysis from the International
      T-cell Lymphoma Project showed that anthracycline-based chemotherapy did not favorably impact
      survival in patients with the most common forms of PTCLs, namely PTCL-NOS and AITL. In a
      retrospective study conducted by the British Columbia cancer agency, the 5-year OS rate for
      patients with PTCL-NOS primarily treated with CHOP or CHOP-like regimens was only 35%; among
      these patients, the 5-year OS rates were higher in patients with low-risk IPI scores compared
      with those with high-risk IPI scores (64% vs. 22%, respectively). In addition, patients with
      ALK-positive ALCL had superior clinical outcome compared to those with ALK-negative ALCL
      (5-year OS 58% vs. 34%, respectively). The addition of etoposide to CHOP (CHOEP regimen)
      compared with CHOP alone was evaluated in a randomized study by the German High-grade NHL
      Study Group (DSHNHL). In relatively young patients with favorable prognosis aggressive NHL
      (age ≤60 years; normal LDH levels), the CHOEP regimen resulted in significantly higher CR
      rate (88% vs. 79%; P=0.003) and 5-year EFS rate (69% vs. 58%; P=0.004). No difference was
      observed in OS outcomes between the regimens. It should also be noted that in this study, the
      majority of patients had B-cell histology, with only 14% diagnosed with T-cell NHL (with 12%
      of patients having ALCL, PTCL-NOS, or AITL histology).36 In an analysis of a large cohort of
      patients with PTCL treated within the DSHNHL trials, patients with ALK- positive ALCL had
      favorable outcomes with CHOP or CHOP with etoposide (CHOEP). Three-year EFS and OS rates were
      76% and 90%, respectively, for patients with ALK-positive ALCL. The corresponding outcomes
      were 50% and 67.5%, respectively, for AITL, 46% and 62%, respectively, for ALK-negative ALCL
      and 41% and 54%, respectively, for PTCL-NOS. Among those with T-cell lymphoma, CHOEP was
      associated with a trend for improved EFS among relatively young patients (age <60 years) and
      is an option for these patients. CHOP-21 appeared to be the standard regimen for patients age
      >60 years, given that the addition of etoposide did not provide an advantage in these older
      patients due to increased toxicity. Among patients with ALK-negative ALCL, AITL and PTCL-NOS,
      those with low-risk IPI scores (IPI <1) had a relatively favorable prognosis; contrastingly,
      patients with higher risk IPI scores derived minimal benefit from CHOP or CHOEP.

      Histone deacetylases (HDACs) are involved in the remodeling of chromatin and play a key role
      in the epigenetic regulation of gene expression. HDACs act as transcription repressors by
      removing acetyl groups from the e-amino- terminus of lysine residues within histones to
      promote tighter winding of DNA around histone proteins. Elevated expression or activity of
      HDACs is implicated in the development and progression of cancer. Inhibition of HDAC enzymes
      results in increased histone acetylation, thereby inducing an open chromatin conformation and
      transcription of previously dormant genes. At least 18 human HDACs have been identified and
      are grouped into four classes. HDAC enzymes class I (HDAC1, 2, 3, and 8), class II (HDAC4, 5,
      7, and 9 as IIa, and HDAC6 and 10 as IIb), and class IV (HDAC11) utilize a zinc-catalyzed
      mechanism for deacetylation of histones and non-histone proteins, whereas class III (SIRT
      1-7) HDACs are NAD+ dependent deacetylase enzymes. Although the precise biological functions
      of individual HDACs are still largely unknown, the importance of HDAC enzymes in the
      malignant phenotype has been most closely associated with Class I HDACs 1-3. In addition,
      Class IIb HDACs 6 and 10 have been found to play a role in the expression and stability of
      tumor angiogenesis gene products.

      The synthesis of small-molecule HDAC inhibitors (HDACi) has been an active focus in the field
      of anticancer drug discovery in recent years. Several different chemical classes of HDACi
      have been described, including hydroxamic acids, carboxylic or short-chain fatty acids,
      cyclic peptides, and benzamides. Examples of each of these classes have entered clinical
      development as antitumor agents. Among them, the hydroxamic acid vorinostat (SAHA) and cyclic
      peptide romidepsin (FK-228) were approved in the United States for the treatment of cutaneous
      T-cell lymphoma, and very recently, romidepsin for peripheral T-cell lymphoma.

      chidamide (CS055/HBI-8000), a new member of the benzamide class of HDACi. Chidamide inhibits
      HDAC1, 2, 3, and 10 in the low nanomolar concentration range with broad spectrum antitumor
      activity in vitro and in vivo. Mechanism studies have demonstrated that chidamide stimulates
      human immune cell-mediated tumor cell killing activity with increased expression of genes and
      proteins involved in natural killer (NK) cell functions.

      Chidamide was found to be a low nanomolar inhibitor of HDAC1, 2, 3, and 10, the HDAC isotypes
      well documented to be associated with the malignant phenotype. Significant and broad spectrum
      in vitro and in vivo anti- tumor activity, including a wide therapeutic index, was observed.
      Chidamide was also shown to enhance the cytotoxic effect of human peripheral mononuclear
      cells ex vivo on K562 target cells, accompanied by the upregulation of proteins involved in
      NK cell functions. Furthermore, the expression of a number of genes involved in immune cell-
      mediated antitumor activity was observed to be upregulated in peripheral white blood cells
      from two T-cell lymphoma patients who responded to chidamide administration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: complete remission rate
time frame: 3 year
measure: disease free survival
time frame: 3 years
measure: overall survival
time frame: 3 years
measure: time to progression
time frame: 3 years
arm group label: chidamide regimen
arm group type: Experimental
description: patients receive chidamide (30mg twice every week) po, cyclophosphamide (750mg/m2) iv on day 1, liposomal doxorubicin (30mg/m2) iv on day 1, vincristine (1.4mg/m2, max to 2mg) iv on day 1 and prednisone (100mg/d) po on day 1-5.
arm group label: CDOP regimen
arm group type: Active Comparator
description: patients receive cyclophosphamide (750mg/m2) iv on day 1, liposomal doxorubicin (30mg/m2) iv on day 1, vincristine (1.4mg/m2, max to 2mg) iv on day 1 and prednisone (100mg/d) po on day 1-5.
intervention type: Drug
intervention name: chidamide
description: 30mg po twice a week
arm group label: chidamide regimen
other name: epidaza
intervention type: Drug
intervention name: cyclophosphamide
description: 750mg/m2 iv on day 1
arm group label: CDOP regimen
arm group label: chidamide regimen
intervention type: Drug
intervention name: liposomal doxorubicin
description: 30mg/m2 iv on day 1
arm group label: CDOP regimen
arm group label: chidamide regimen
intervention type: Drug
intervention name: vincristine
description: 1.4mg/m2 iv on day 1
arm group label: CDOP regimen
arm group label: chidamide regimen
intervention type: Drug
intervention name: prednisone
description: 100mg/d po on day 1-5
arm group label: CDOP regimen
arm group label: chidamide regimen
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ru Feng, M.D.
role: Study Chair
affiliation: Department of Hematology Nanfang Hospital, The Southern Medical University
last name: Ru Feng, M.D.
phone: +86 13725119762
phone ext: 510515
email: ruth1626@hotmail.com
last name: Qi Wei, M.D.
phone: +86 13427564102
phone ext: 510515
email: sinbad37@126.com
facility: 
contact: 
contact backup: 
investigator: 
country: China
url: http://www.nfyy.com/
description: Nan fang Hospital, the Southern Medical University
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: Principal Investigator
investigator affiliation: Nanfang Hospital, Southern Medical University
investigator full name: Ru Feng
investigator title: Professor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Vincristine
sharing ipd: No