<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/NCT03837873</url>
  </required_header>
  <id_info>
    <org_study_id>IIT2018010-EC-2</org_study_id>
    <nct_id>NCT03837873</nct_id>
  </id_info>
  <brief_title>DLCL002 Protocol for Patients With High Risk Aggressive B-cell Lymphoma</brief_title>
  <official_title>DLCL002 Protocol for Young Patients With Newly Diagnosed High Risk Aggressive B-cell Lymphoma, a Multicenter Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Hematology &amp; Blood Diseases Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Hematology &amp; Blood Diseases Hospital, China</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Patients eligible for the study will receive R-DA-EDOCH as the induction therapy and be&#xD;
      evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET(Deauville&#xD;
      score 1-3) will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those&#xD;
      achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP and then be&#xD;
      revaluated by the second interim-PET. Patients who achieved CR+good PR(Deauville score 4)&#xD;
      after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville&#xD;
      score 5) will receive other rescue treatments(including ASCT+CAR T).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Survival for patients with high risk aggressive B-cell lymphoma is still unsatisfied.&#xD;
      Dose-intensified immunochemotherapy might improve the outcome. But for patients who could not&#xD;
      achieve CR after the dose-intensified induction therapy, the prognosis is poor. The DLCL002&#xD;
      protocol is a total therapy which including induction therapy, rescue therapy and autologous&#xD;
      stem cell transplantation. Patients eligible for the study will receive R-DA-EDOCH as the&#xD;
      induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at&#xD;
      interim-PET(Deauville score 1-3) will receive either ASCT or the remaining 4 cycles of&#xD;
      R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of&#xD;
      R(2)-DHAP and then be revaluated by the second interim-PET. Patients who achieved CR+good&#xD;
      PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those&#xD;
      remain in PR(Deauville score 5) will receive other rescue treatments(including ASCT+CAR T).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS</measure>
    <time_frame>From the date of the start of treatment until the date of first documented progression, relapse or death from any cause, whichever came first, assessed up to 2 years.</time_frame>
    <description>progression free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR</measure>
    <time_frame>up to 3 months after the end of the therapy</time_frame>
    <description>objective response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EFS</measure>
    <time_frame>From the date of the start of treatment until the date of the ﬁrst adverse event (i.e. disease progression, relapse, diagnosis of a secondary malignancy, institution of a new anticancer treatment, any cause of death), assessed up to 2 years.</time_frame>
    <description>event free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>From the date of the start of treatment until the date of death from any cause, assessed up to 2 years.</time_frame>
    <description>overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRR</measure>
    <time_frame>up to 3 months after the end of the therapy</time_frame>
    <description>complete response rate</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">118</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <condition>High-grade B-cell Lymphoma</condition>
  <condition>Transformed Lymphoma</condition>
  <arm_group>
    <arm_group_label>DLCL002 protocol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive R-DA-EDOCH(rituximab, etoposide, dexamethasone, vincristine, cyclophosphamide, doxorubicin) as induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP(rituximab, lenalidomide(only for patients with non-GCB DLBCL), dexamethasone, cisplatin, cytarabine). Patients who achieved CR+good PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville score 5) will receive other rescue treatments.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>rituximab 750mg/m2 i.v. on day 0</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>50mg/m2, continuous i.v. on day 1-4</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>0.4mg/m2, continuous i.v. on day 1-4</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>10mg/m2, continuous i.v. on day 1-4</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>30mg/day, i.v. on day 1-5 for R-DA-EDOCH regimen; 40mg/day, i.v. on day 1-4 for R(2)-DHAP regimen</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>750mg/m2, i.v. on day5</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>25mg/day, p.o. on day 0-9</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>100mg/m2 continuous i.v. on day 1</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>2g/m2 q12h, i.v. on day 2</description>
    <arm_group_label>DLCL002 protocol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological confirmed aggressive B-cell lymphoma with one of the following subtypes:&#xD;
&#xD;
               1. diffuse large B-cell lymphoma, NOS with at least one poor prognostic factor as&#xD;
                  follows:&#xD;
&#xD;
                    1. aaIPI 2~3(≤60 years) or IPI 3~5(&gt;60 years);&#xD;
&#xD;
                    2. double protein expression lymphoma(IHC MYC≥40% and BCL2≥50%） with Ann Arbor&#xD;
                       stage of III~IV or aaIPI 2~3 or IPI 3~5;&#xD;
&#xD;
                    3. CD5+ DLBCL.&#xD;
&#xD;
               2. high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;&#xD;
&#xD;
               3. high-grade B-cell lymphoma, NOS&#xD;
&#xD;
               4. transformed lymphoma(no prior treatment)&#xD;
&#xD;
          -  Age 18 to 65 years&#xD;
&#xD;
          -  ECOG-PS: 0~2&#xD;
&#xD;
          -  Life-expectancy &gt; 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with central nerves system involvement&#xD;
&#xD;
          -  HIV positivity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dehui Zou, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei Liu, Dr.</last_name>
    <phone>+86-020-23909282</phone>
    <email>liuwei@ihcams.ac.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hunan Cancer Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Hui Zhou, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Hui Zhou, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>the First Affiliated Hospital of Nanchang University</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Fei Li, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Fei Li, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>the First Affiliated Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Fengyan Jin, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Fengyan Jin, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>the Second Hospital of Dalian Medical University</name>
      <address>
        <city>Dalian</city>
        <state>Liaoning</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Xiaobo Wang, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Xiaobo Wang, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Qingdao Central Hospital</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ling Wang, Dr.</last_name>
    </contact>
    <investigator>
      <last_name>Ling Wang, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institute of Hematology &amp; Blood Diseases Hospital</name>
      <address>
        <city>Tianjin</city>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wei Liu, Dr.</last_name>
      <phone>86-022-23909282</phone>
      <email>liuwei@ihcams.ac.cn</email>
    </contact>
    <investigator>
      <last_name>Dehui Zou, Dr.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wei Liu, Dr.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>January 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>January 24, 2022</last_update_submitted>
  <last_update_submitted_qc>January 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Institute of Hematology &amp; Blood Diseases Hospital, China</investigator_affiliation>
    <investigator_full_name>Zou Dehui</investigator_full_name>
    <investigator_title>principal 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, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03837873
org study id: IIT2018010-EC-2
nct id: NCT03837873
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients eligible for the study will receive R-DA-EDOCH as the induction therapy and be
      evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET(Deauville
      score 1-3) will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those
      achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP and then be
      revaluated by the second interim-PET. Patients who achieved CR+good PR(Deauville score 4)
      after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville
      score 5) will receive other rescue treatments(including ASCT+CAR T).
Survival for patients with high risk aggressive B-cell lymphoma is still unsatisfied.
      Dose-intensified immunochemotherapy might improve the outcome. But for patients who could not
      achieve CR after the dose-intensified induction therapy, the prognosis is poor. The DLCL002
      protocol is a total therapy which including induction therapy, rescue therapy and autologous
      stem cell transplantation. Patients eligible for the study will receive R-DA-EDOCH as the
      induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at
      interim-PET(Deauville score 1-3) will receive either ASCT or the remaining 4 cycles of
      R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of
      R(2)-DHAP and then be revaluated by the second interim-PET. Patients who achieved CR+good
      PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those
      remain in PR(Deauville score 5) will receive other rescue treatments(including ASCT+CAR T).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: From the date of the start of treatment until the date of first documented progression, relapse or death from any cause, whichever came first, assessed up to 2 years.
description: progression free survival
measure: ORR
time frame: up to 3 months after the end of the therapy
description: objective response rate
measure: EFS
time frame: From the date of the start of treatment until the date of the ﬁrst adverse event (i.e. disease progression, relapse, diagnosis of a secondary malignancy, institution of a new anticancer treatment, any cause of death), assessed up to 2 years.
description: event free survival
measure: OS
time frame: From the date of the start of treatment until the date of death from any cause, assessed up to 2 years.
description: overall survival
measure: CRR
time frame: up to 3 months after the end of the therapy
description: complete response rate
arm group label: DLCL002 protocol
arm group type: Experimental
description: Patients will receive R-DA-EDOCH(rituximab, etoposide, dexamethasone, vincristine, cyclophosphamide, doxorubicin) as induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP(rituximab, lenalidomide(only for patients with non-GCB DLBCL), dexamethasone, cisplatin, cytarabine). Patients who achieved CR+good PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville score 5) will receive other rescue treatments.
intervention type: Drug
intervention name: Rituximab
description: rituximab 750mg/m2 i.v. on day 0
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Etoposide
description: 50mg/m2, continuous i.v. on day 1-4
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Vincristine
description: 0.4mg/m2, continuous i.v. on day 1-4
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Doxorubicin
description: 10mg/m2, continuous i.v. on day 1-4
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Dexamethasone
description: 30mg/day, i.v. on day 1-5 for R-DA-EDOCH regimen; 40mg/day, i.v. on day 1-4 for R(2)-DHAP regimen
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Cyclophosphamide
description: 750mg/m2, i.v. on day5
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Lenalidomide
description: 25mg/day, p.o. on day 0-9
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Cisplatin
description: 100mg/m2 continuous i.v. on day 1
arm group label: DLCL002 protocol
intervention type: Drug
intervention name: Cytarabine
description: 2g/m2 q12h, i.v. on day 2
arm group label: DLCL002 protocol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dehui Zou, Dr.
role: Principal Investigator
affiliation: Institute of Hematology & Blood Diseases Hospital, China
last name: Wei Liu, Dr.
phone: +86-020-23909282
email: liuwei@ihcams.ac.cn
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Institute of Hematology & Blood Diseases Hospital, China
investigator full name: Zou Dehui
investigator title: principal investigator
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Cytarabine
mesh term: Dexamethasone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Doxorubicin
mesh term: Etoposide
mesh term: Vincristine
mesh term: Lenalidomide
sharing ipd: Undecided