<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/NCT04432714</url>
  </required_header>
  <id_info>
    <org_study_id>2019-SR-430</org_study_id>
    <nct_id>NCT04432714</nct_id>
  </id_info>
  <brief_title>Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement</brief_title>
  <official_title>A Phase II, Prospective, Single-center Study of Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The First Affiliated Hospital with Nanjing Medical University</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>
      The prognosis of DLBCL with MYC rearrangement is dismal. Previous study showed that&#xD;
      lenalidomide in combination with R-CHOP showed promising therapeutic activity and that R-DA&#xD;
      EPOCH was superior compared to R-CHOP regimen in this cohort of patients. The investigators&#xD;
      therefore design this phase I/II study to investigate the safety and efficacy of lenalidomide&#xD;
      in combination with R-DA EPOCH in patients with untreated MYC-rearranged DLBCL.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">June 9, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>maximum tolerated dose and dose limited toxicity</measure>
    <time_frame>21 days after first cycle of R2-DA-EPOCH regimen (each cycle is 21 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progressive free survival</measure>
    <time_frame>2 years</time_frame>
    <description>from date of inclusion to date of progression, relapse, or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>from the date of inclusion to date of death, irrespective of cause</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">81</enrollment>
  <condition>DLBCL</condition>
  <condition>Untreated</condition>
  <condition>MYC Gene Rearrangement</condition>
  <arm_group>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Lenalidomide 10mg/d#15mg/d#20mg/d#25mg/d d1~d10# 21days a cycle</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituximab 375 mg/m2，IV, d0</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Etoposide 50 mg/m2/day CI24h d1-d4</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Doxorubicin 10 mg/m2/day CI24h d1-d4</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Vincristine 0.4mg/m2/day CI24h d1-d4</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Cyclophosphamide 750 mg/m2/day IV d5</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Prednisone 60 mg/m2/bid oral or IV d1-d5</description>
    <arm_group_label>R2-DA-EPOCH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed DLBCL with MYC rearrangement according to WHO 2016 criteria,&#xD;
             excluding PMBCL, PCNSL, HIV-associated lymphoma.&#xD;
&#xD;
          2. ECOG PS 0-2&#xD;
&#xD;
          3. Age 18-60 years old&#xD;
&#xD;
          4. Expected survival ≥ 12 weeks&#xD;
&#xD;
          5. A measurable or evaluable disease at the time of enrolment (diameter ≥1.5cm)&#xD;
&#xD;
          6. Understand and voluntarily sign an informed consent form, able to adhere to the study&#xD;
             visit schedule and other protocol requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who are pregnant or lactating. Patients have breeding intent in 12 months or&#xD;
             cannot take effective contraceptive measures during the trial measures&#xD;
&#xD;
          2. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital&#xD;
             immune deficiency diseases, including but not limited to HIV infected persons&#xD;
&#xD;
          3. Previous exposure to any anti-tumor therapy&#xD;
&#xD;
          4. Poor hepatic and/or renal function, defined as total bilirubin, ALT, AST, Cr more than&#xD;
             two fold of upper normal level,Ccr# 50 mL/min unless these abnormalities were related&#xD;
             to the lymphoma&#xD;
&#xD;
          5. History of DVT or PE within past 12 months&#xD;
&#xD;
          6. Poor bone-marrow reserve, defined as neutrophil count less than 1.5×109/L or platelet&#xD;
             count less than 75×109/L, unless caused by bone marrow infiltration&#xD;
&#xD;
          7. New York Heart Association class III or IV cardiac failure; or Ejection fraction less&#xD;
             than 50%;or history of following disease in past 6 months: acute coronary&#xD;
             syndrome#acute heart failure#severe ventricular arrhythmia&#xD;
&#xD;
          8. CNS or meningeal involvement&#xD;
&#xD;
          9. Known sensitivity or allergy to investigational product&#xD;
&#xD;
         10. Major surgery within three weeks&#xD;
&#xD;
         11. Patients receiving organ transplantation&#xD;
&#xD;
         12. Patients with secondary tumour, excluding cured (5 years without relapse) in situ&#xD;
             Non-melanoma skin cancer. superficial bladder cancer, in situ cervical cancer,&#xD;
             Gastrointestinal intramucous carcinoma and breast cancer&#xD;
&#xD;
         13. Presence of Grade III nervous toxicity within past two weeks&#xD;
&#xD;
         14. Active and severe infectious diseases&#xD;
&#xD;
         15. Any potential drug abuse, medical, psychological or social conditions whichmay disturb&#xD;
             this investigation and assessment&#xD;
&#xD;
         16. In any conditions which investigator considered ineligible for this study&#xD;
&#xD;
         17. Patients with histological transformation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Xu, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Li Wang, M.D., Ph.D</last_name>
    <phone>86 25 68306034</phone>
    <email>lilyw7878@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wei Xu, M.D., Ph.D</last_name>
    <phone>86 25 68306034</phone>
    <email>xuwei10000@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Wang, M.D., Ph.D</last_name>
      <phone>86 25 68306034</phone>
      <email>lilyw7878@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Godfrey JK, Nabhan C, Karrison T, Kline JP, Cohen KS, Bishop MR, Stadler WM, Karmali R, Venugopal P, Rapoport AP, Smith SM. Phase 1 study of lenalidomide plus dose-adjusted EPOCH-R in patients with aggressive B-cell lymphomas with deregulated MYC and BCL2. Cancer. 2019 Jun 1;125(11):1830-1836. doi: 10.1002/cncr.31877. Epub 2019 Feb 1.</citation>
    <PMID>30707764</PMID>
  </reference>
  <reference>
    <citation>Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):366-378. doi: 10.1182/asheducation-2016.1.366.</citation>
    <PMID>27913503</PMID>
  </reference>
  <reference>
    <citation>Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, Parekh S, Lacasce A, Hayslip JW, Jagadeesh D, Nagpal S, Lechowicz MJ, Gaur R, Lucas A, Melani C, Roschewski M, Steinberg SM, Jaffe ES, Kahl B, Friedberg JW, Little RF, Bartlett NL, Wilson WH. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet Haematol. 2018 Dec;5(12):e609-e617. doi: 10.1016/S2352-3026(18)30177-7.</citation>
    <PMID>30501868</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 13, 2020</last_update_submitted>
  <last_update_submitted_qc>June 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The First Affiliated Hospital with Nanjing Medical University</investigator_affiliation>
    <investigator_full_name>WEI XU</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>DLBCL</keyword>
  <keyword>MYC Gene rearrangement</keyword>
  <keyword>Lenalidomide</keyword>
  <keyword>R-DA EPOCH</keyword>
  <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>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/NCT04432714
org study id: 2019-SR-430
nct id: NCT04432714
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The prognosis of DLBCL with MYC rearrangement is dismal. Previous study showed that
      lenalidomide in combination with R-CHOP showed promising therapeutic activity and that R-DA
      EPOCH was superior compared to R-CHOP regimen in this cohort of patients. The investigators
      therefore design this phase I/II study to investigate the safety and efficacy of lenalidomide
      in combination with R-DA EPOCH in patients with untreated MYC-rearranged DLBCL.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: maximum tolerated dose and dose limited toxicity
time frame: 21 days after first cycle of R2-DA-EPOCH regimen (each cycle is 21 days)
measure: Overall response rate
time frame: 6 months
measure: Progressive free survival
time frame: 2 years
description: from date of inclusion to date of progression, relapse, or death from any cause
measure: Overall survival
time frame: 2 years
description: from the date of inclusion to date of death, irrespective of cause
arm group label: R2-DA-EPOCH
arm group type: Experimental
intervention type: Drug
intervention name: Lenalidomide
description: Lenalidomide 10mg/d#15mg/d#20mg/d#25mg/d d1~d10# 21days a cycle
arm group label: R2-DA-EPOCH
intervention type: Drug
intervention name: Rituximab
description: Rituximab 375 mg/m2，IV, d0
arm group label: R2-DA-EPOCH
intervention type: Drug
intervention name: Etoposide
description: Etoposide 50 mg/m2/day CI24h d1-d4
arm group label: R2-DA-EPOCH
intervention type: Drug
intervention name: Doxorubicin
description: Doxorubicin 10 mg/m2/day CI24h d1-d4
arm group label: R2-DA-EPOCH
intervention type: Drug
intervention name: Vincristine
description: Vincristine 0.4mg/m2/day CI24h d1-d4
arm group label: R2-DA-EPOCH
intervention type: Drug
intervention name: Cyclophosphamide
description: Cyclophosphamide 750 mg/m2/day IV d5
arm group label: R2-DA-EPOCH
intervention type: Drug
intervention name: Prednisone
description: Prednisone 60 mg/m2/bid oral or IV d1-d5
arm group label: R2-DA-EPOCH
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Wei Xu, M.D., Ph.D
role: Principal Investigator
affiliation: The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
last name: Li Wang, M.D., Ph.D
phone: 86 25 68306034
email: lilyw7878@163.com
last name: Wei Xu, M.D., Ph.D
phone: 86 25 68306034
email: xuwei10000@hotmail.com
facility: 
status: Recruiting
contact: 
country: China
citation: Godfrey JK, Nabhan C, Karrison T, Kline JP, Cohen KS, Bishop MR, Stadler WM, Karmali R, Venugopal P, Rapoport AP, Smith SM. Phase 1 study of lenalidomide plus dose-adjusted EPOCH-R in patients with aggressive B-cell lymphomas with deregulated MYC and BCL2. Cancer. 2019 Jun 1;125(11):1830-1836. doi: 10.1002/cncr.31877. Epub 2019 Feb 1.
PMID: 30707764
citation: Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):366-378. doi: 10.1182/asheducation-2016.1.366.
PMID: 27913503
citation: Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, Parekh S, Lacasce A, Hayslip JW, Jagadeesh D, Nagpal S, Lechowicz MJ, Gaur R, Lucas A, Melani C, Roschewski M, Steinberg SM, Jaffe ES, Kahl B, Friedberg JW, Little RF, Bartlett NL, Wilson WH. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet Haematol. 2018 Dec;5(12):e609-e617. doi: 10.1016/S2352-3026(18)30177-7.
PMID: 30501868
responsible party type: Principal Investigator
investigator affiliation: The First Affiliated Hospital with Nanjing Medical University
investigator full name: WEI XU
investigator title: Professor
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Doxorubicin
mesh term: Etoposide
mesh term: Vincristine
mesh term: Lenalidomide
sharing ipd: Undecided