<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/NCT03016000</url>
  </required_header>
  <id_info>
    <org_study_id>NFL2016-B2</org_study_id>
    <nct_id>NCT03016000</nct_id>
  </id_info>
  <brief_title>Thalidomide Maintenance Treatment in DLBCL</brief_title>
  <official_title>A Multicentre, Randomized Phase III Study of Thalidomide Maintenance Treatment in Patients With Diffuse Large B-cell Lymphoma</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, multi-center,phase III study to evaluate the ability of thalidomide&#xD;
      maintenance therapy to prolong relapse-free survival in diffuse large B cell lymphoma(DLBCL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, phase III study to evaluate the ability of thalidomide maintenance&#xD;
      therapy to prolong relapse-free survival(RFS), in diffuse large B cell&#xD;
      lymphoma(DLBCL).Patients will be enrolled after successful standard induction therapy (CR or&#xD;
      CRu following standard R-CHOP-like therapy with 8 infusions of rituximab plus CHOP-like&#xD;
      chemotherapy (4-8 cycles). Patients will be followed until an event occurs as defined in the&#xD;
      protocol. To evaluate the clinical efficacy of thalidomide maintenance therapy as compared to&#xD;
      observation in patients with DLBCL who have achieved a complete remission after appropriate&#xD;
      first-line therapy, measured by RFS, 226 patients with DLCBL will be recruited.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 26, 2017</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 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>Relapse-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>RFS was defined as the time between randomization and any documentation of relapse, death by any cause or last follow up.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>OS was defined as the interval from randomization to death or the last follow-up for surviving patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events</measure>
    <time_frame>5 years</time_frame>
    <description>Adverse events were classified as defined by the National Cancer Institute Common Toxicity Criteria, version 2. Safety evaluations were focused especially on neurological symptoms and the development of deep venous thrombosis (DVT).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">226</enrollment>
  <condition>Lymphoma, Large B-Cell, Diffuse</condition>
  <arm_group>
    <arm_group_label>Thalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thalidomide 50mg daily by mouth( increase 50mg after 2 weeks if tolerated until 200mg/day) until disease progression or intolerance due to AEs.The dose could be reduced if the patient experienced grade 2 or higher AEs. Does reductions for AEs were recommended (200 mg daily to 100 mg daily, 100 mg daily to 50 mg daily).In patients intolerant of 50mg/day, thalidomide discontinuation was allowed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Observation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thalidomide</intervention_name>
    <description>Thalidomide 50mg daily by mouth( increase 25mg after 2 weeks if tolerated Until 200mg/day) until disease progression or intolerance due to AEs.The dose could be reduced if patient experienced grade 2 or higher AEs. Does reductions for AEs were recommended (200 mg daily to 100 mg daily, 100 mg daily to 50 mg daily).In patients intolerant of 50mg/ day, thalidomide discontinuation was allowed.</description>
    <arm_group_label>Thalidomide</arm_group_label>
    <other_name>Thalomid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Observation</intervention_name>
    <description>Just observation</description>
    <arm_group_label>Observation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  NCCN-IPI&gt;1,&#xD;
&#xD;
          -  Known IPI, cell of origin and DHL at time of diagnosis,&#xD;
&#xD;
          -  Negative pregnancy test,&#xD;
&#xD;
          -  Men must agree not to father a child during the therapy,&#xD;
&#xD;
          -  6 to 8 cycles R-CHOP/like, total of 8 x Rituximab,&#xD;
&#xD;
          -  CR, CRu&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Transformed lymphoma,&#xD;
&#xD;
          -  Secondary malignancy,&#xD;
&#xD;
          -  HIV positive,&#xD;
&#xD;
          -  Evidence of CNS involvement,&#xD;
&#xD;
          -  Cardiac dysfunction (systolic ejection fraction &lt;50%),&#xD;
&#xD;
          -  Creatinine &gt; 2.0 mg/dl&#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>Ru Feng, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Hematology, Nanfang Hospital, Southern Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ru Feng, M.D.</last_name>
    <phone>86-20-61641613</phone>
    <email>ruth1626@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xiaolei Wei, Ph.D.</last_name>
    <phone>86-20-61641613</phone>
    <email>smuxiaoleiwei@163.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>
    <status>Recruiting</status>
    <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>
  <reference>
    <citation>Chaganti S, Illidge T, Barrington S, Mckay P, Linton K, Cwynarski K, McMillan A, Davies A, Stern S, Peggs K; British Committee for Standards in Haematology. Guidelines for the management of diffuse large B-cell lymphoma. Br J Haematol. 2016 Jul;174(1):43-56. doi: 10.1111/bjh.14136. Epub 2016 May 16. No abstract available.</citation>
    <PMID>27196701</PMID>
  </reference>
  <reference>
    <citation>Michallet AS, Lebras L, Coiffier B. Maintenance therapy in diffuse large B-cell lymphoma. Curr Opin Oncol. 2012 Sep;24(5):461-5. doi: 10.1097/CCO.0b013e3283562036.</citation>
    <PMID>22759738</PMID>
  </reference>
  <reference>
    <citation>Aviles A, Cleto S, Huerta-Guzman J, Neri N. Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP-BLEO regimens. Eur J Haematol. 2001 Feb;66(2):94-9. doi: 10.1034/j.1600-0609.2001.00272.x.</citation>
    <PMID>11168516</PMID>
  </reference>
  <reference>
    <citation>Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Duhrsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Briere J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. doi: 10.1200/JCO.2012.41.9416. Epub 2012 Oct 22.</citation>
    <PMID>23091101</PMID>
  </reference>
  <reference>
    <citation>Crump M, Leppa S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T. Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2016 Jul 20;34(21):2484-92. doi: 10.1200/JCO.2015.65.7171. Epub 2016 May 23.</citation>
    <PMID>27217449</PMID>
  </reference>
  <reference>
    <citation>Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Kramer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. doi: 10.1111/bjh.13652. Epub 2015 Oct 9.</citation>
    <PMID>26449739</PMID>
  </reference>
  <reference>
    <citation>Ji D, Li Q, Cao J, Guo Y, Lv F, Liu X, Wang B, Wang L, Luo Z, Chang J, Wu X, Hong X. Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: A phase II study. Oncotarget. 2016 May 31;7(22):33331-9. doi: 10.18632/oncotarget.8973.</citation>
    <PMID>27129176</PMID>
  </reference>
  <reference>
    <citation>Maiolino A, Hungria VT, Garnica M, Oliveira-Duarte G, Oliveira LC, Mercante DR, Miranda EC, Quero AA, Peres AL, Barros JC, Tanaka P, Magalhaes RP, Rego EM, Lorand-Metze I, Lima CS, Renault IZ, Braggio E, Chiattone C, Nucci M, de Souza CA; Brazilian Multiple Myeloma Study Group (BMMSG/GEMOH). Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma. Am J Hematol. 2012 Oct;87(10):948-52. doi: 10.1002/ajh.23274. Epub 2012 Jun 23.</citation>
    <PMID>22730113</PMID>
  </reference>
  <reference>
    <citation>Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, Gill DS, Horvath N, Reynolds J, Kennedy N. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009 Apr 10;27(11):1788-93. doi: 10.1200/JCO.2008.18.8573. Epub 2009 Mar 9.</citation>
    <PMID>19273705</PMID>
  </reference>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>November 2, 2016</study_first_submitted>
  <study_first_submitted_qc>January 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>July 26, 2017</last_update_submitted>
  <last_update_submitted_qc>July 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 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>diffuse large B-cell lymphoma</keyword>
  <keyword>Thalidomide</keyword>
  <keyword>Maintenance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</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>Thalidomide</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03016000
org study id: NFL2016-B2
nct id: NCT03016000
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a randomized, multi-center,phase III study to evaluate the ability of thalidomide
      maintenance therapy to prolong relapse-free survival in diffuse large B cell lymphoma(DLBCL).
This is a randomized, phase III study to evaluate the ability of thalidomide maintenance
      therapy to prolong relapse-free survival(RFS), in diffuse large B cell
      lymphoma(DLBCL).Patients will be enrolled after successful standard induction therapy (CR or
      CRu following standard R-CHOP-like therapy with 8 infusions of rituximab plus CHOP-like
      chemotherapy (4-8 cycles). Patients will be followed until an event occurs as defined in the
      protocol. To evaluate the clinical efficacy of thalidomide maintenance therapy as compared to
      observation in patients with DLBCL who have achieved a complete remission after appropriate
      first-line therapy, measured by RFS, 226 patients with DLCBL will be recruited.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Relapse-free survival
time frame: 5 years
description: RFS was defined as the time between randomization and any documentation of relapse, death by any cause or last follow up.
measure: Overall survival
time frame: 5 years
description: OS was defined as the interval from randomization to death or the last follow-up for surviving patients.
measure: Incidence of treatment-emergent adverse events
time frame: 5 years
description: Adverse events were classified as defined by the National Cancer Institute Common Toxicity Criteria, version 2. Safety evaluations were focused especially on neurological symptoms and the development of deep venous thrombosis (DVT).
arm group label: Thalidomide
arm group type: Experimental
description: Thalidomide 50mg daily by mouth( increase 50mg after 2 weeks if tolerated until 200mg/day) until disease progression or intolerance due to AEs.The dose could be reduced if the patient experienced grade 2 or higher AEs. Does reductions for AEs were recommended (200 mg daily to 100 mg daily, 100 mg daily to 50 mg daily).In patients intolerant of 50mg/day, thalidomide discontinuation was allowed.
arm group label: Observation
arm group type: Other
description: Observation
intervention type: Drug
intervention name: Thalidomide
description: Thalidomide 50mg daily by mouth( increase 25mg after 2 weeks if tolerated Until 200mg/day) until disease progression or intolerance due to AEs.The dose could be reduced if patient experienced grade 2 or higher AEs. Does reductions for AEs were recommended (200 mg daily to 100 mg daily, 100 mg daily to 50 mg daily).In patients intolerant of 50mg/ day, thalidomide discontinuation was allowed.
arm group label: Thalidomide
other name: Thalomid
intervention type: Other
intervention name: Observation
description: Just observation
arm group label: Observation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Ru Feng, M.D.
role: Principal Investigator
affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University
last name: Ru Feng, M.D.
phone: 86-20-61641613
email: ruth1626@hotmail.com
last name: Xiaolei Wei, Ph.D.
phone: 86-20-61641613
email: smuxiaoleiwei@163.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
citation: Chaganti S, Illidge T, Barrington S, Mckay P, Linton K, Cwynarski K, McMillan A, Davies A, Stern S, Peggs K; British Committee for Standards in Haematology. Guidelines for the management of diffuse large B-cell lymphoma. Br J Haematol. 2016 Jul;174(1):43-56. doi: 10.1111/bjh.14136. Epub 2016 May 16. No abstract available.
PMID: 27196701
citation: Michallet AS, Lebras L, Coiffier B. Maintenance therapy in diffuse large B-cell lymphoma. Curr Opin Oncol. 2012 Sep;24(5):461-5. doi: 10.1097/CCO.0b013e3283562036.
PMID: 22759738
citation: Aviles A, Cleto S, Huerta-Guzman J, Neri N. Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP-BLEO regimens. Eur J Haematol. 2001 Feb;66(2):94-9. doi: 10.1034/j.1600-0609.2001.00272.x.
PMID: 11168516
citation: Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Duhrsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Briere J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. doi: 10.1200/JCO.2012.41.9416. Epub 2012 Oct 22.
PMID: 23091101
citation: Crump M, Leppa S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T. Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2016 Jul 20;34(21):2484-92. doi: 10.1200/JCO.2015.65.7171. Epub 2016 May 23.
PMID: 27217449
citation: Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Kramer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. doi: 10.1111/bjh.13652. Epub 2015 Oct 9.
PMID: 26449739
citation: Ji D, Li Q, Cao J, Guo Y, Lv F, Liu X, Wang B, Wang L, Luo Z, Chang J, Wu X, Hong X. Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: A phase II study. Oncotarget. 2016 May 31;7(22):33331-9. doi: 10.18632/oncotarget.8973.
PMID: 27129176
citation: Maiolino A, Hungria VT, Garnica M, Oliveira-Duarte G, Oliveira LC, Mercante DR, Miranda EC, Quero AA, Peres AL, Barros JC, Tanaka P, Magalhaes RP, Rego EM, Lorand-Metze I, Lima CS, Renault IZ, Braggio E, Chiattone C, Nucci M, de Souza CA; Brazilian Multiple Myeloma Study Group (BMMSG/GEMOH). Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression-free survival in multiple myeloma. Am J Hematol. 2012 Oct;87(10):948-52. doi: 10.1002/ajh.23274. Epub 2012 Jun 23.
PMID: 22730113
citation: Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, Gill DS, Horvath N, Reynolds J, Kennedy N. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009 Apr 10;27(11):1788-93. doi: 10.1200/JCO.2008.18.8573. Epub 2009 Mar 9.
PMID: 19273705
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, Large B-Cell, Diffuse
mesh term: Thalidomide