<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/NCT04481815</url>
  </required_header>
  <id_info>
    <org_study_id>IR2020001238</org_study_id>
    <nct_id>NCT04481815</nct_id>
  </id_info>
  <brief_title>Rituximab Plus Methotrexate With or Without Lenalidomide in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma</brief_title>
  <official_title>Efficacy and Safety Study of Lenalidomide Plus Rituximab and Methotrexate Chemotherapy（R2-MTX） Versus Rituximab and Methotrexate Chemotherapy（R-MTX） in Newly Diagnosed Primary Central Nervous System Lymphoma: a Multicenter, Open-Label, Randomised Phase 2 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Second Affiliated Hospital, School of Medicine, Zhejiang University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is a multicenter, open-Label, randomised phase 2 study to compare the efficacy and safety&#xD;
      study of R2-MTX chemotherapy（Lenalidomide, Rituximab and Methotrexate）with R-MTX&#xD;
      chemotherapy（Rituximab and Methotrexate ）as first-line regimens in the treatment of newly&#xD;
      diagnosed primary central nervous system lymphoma.2-year Progression free survival (PFS) is&#xD;
      the primary endpoint.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-Label, randomised phase 2 study designed to evaluate the efficacy&#xD;
      and safety of rituximab plus methotrexate with or without lenalidomide as first-line regimens&#xD;
      in the treatment of primary central nervous system lymphoma. A total of 240 patients plan to&#xD;
      participate in this study to receive a total 6 cycles of induction chemotherapy followed by 4&#xD;
      cycles of maintenance chemotherapy. Follow-ups should be taken up to the first 3 years.The&#xD;
      primary endpoints were 2-year PFS rate and and secondary endpoints including objective&#xD;
      response rate (ORR), PFS, overall survival (OS), and adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</primary_completion_date>
  <phase>Phase 2</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>2-year progression free survival</measure>
    <time_frame>2 years</time_frame>
    <description>From date of patients sign informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>At the end of Cycle 6 chemotheray</time_frame>
    <description>At the end of Cycle 6 (each cycle is 21 days) the ratio of numbers of patients with complete response and partial response to all the participants receiving treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>3 years</time_frame>
    <description>From date of patients sign informed consent until the date of death or the date of last follow-up time, whichever came first, assessed up to 3 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>3 years</time_frame>
    <description>From date of patients sign informed consent until the date of progression or death or the date of last follow-up time, whichever came first, assessed up to 3 years</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-related adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Serum ctDNA biomarkers and tissue biomarkers</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Next generation sequencing of serum and tissue samples to identify circulating tumor DNA（ctDNA）and tissue biomarkers before and after treatment</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>PCNSL</condition>
  <arm_group>
    <arm_group_label>R2-MTX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental arm will be treated with R2-MTX regimen(Lenalidomide plus Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved complete remission（CR）or partial remission（PR）with additional whole-brain radiotherapy（WBRT）, they processed to R2 maintenance(Lenalidomide plus Rituximab) for 4 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>R-MTX</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Control arm will be treated with R-MTX regimen(Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved CR or PR with additional WBRT, they processed to Lenalidomide maintenance for 4 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>375mg/m2 intravenous infusion d1, every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 375mg/m2 intravenous infusion d1, every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy.</description>
    <arm_group_label>R-MTX</arm_group_label>
    <arm_group_label>R2-MTX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>25mg orally d1-10 every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 25mg orally d1-14,d29-42 every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy.</description>
    <arm_group_label>R2-MTX</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle, 6 cycles will be prescribed.</description>
    <arm_group_label>R-MTX</arm_group_label>
    <arm_group_label>R2-MTX</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma&#xD;
&#xD;
          2. Age range 18-75 years old.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group performance status 0 to 3.&#xD;
&#xD;
          4. Previously untreated. Patients treated with steroid alone are eligible.&#xD;
&#xD;
          5. Patient's who are not planned to undergo consolidation with autologous hematopoietic&#xD;
             stem cell transplantation（HSCT）.&#xD;
&#xD;
          6. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI.&#xD;
&#xD;
          7. Life expectancy of ≥ 3 months (in the opinion of the investigator).&#xD;
&#xD;
          8. Participants must be able to understand and be willing to sign a written informed&#xD;
             consent document.&#xD;
&#xD;
          9. Women of reproductive potential must agree to use highly effective methods of birth&#xD;
             control during the period of therapy and for 6 months after the last dose of the study&#xD;
             drug. Men who are sexually active must agree to use highly effective contraception&#xD;
             during the period of therapy and for 6 months after the last dose.&#xD;
&#xD;
         10. Women of childbearing potential must have a negative plasma pregnancy test upon study&#xD;
             entry.&#xD;
&#xD;
         11. Adequate renal function: Estimated glomerular filtration rate (GFR) or estimated&#xD;
             creatinine clearance (CrCl) ≥ 50 mL/min;Serum creatinine ≤ 2 times the upper limit of&#xD;
             normal.&#xD;
&#xD;
         12. Adequate liver functions: Transaminase (AST/ALT) &lt; 3 X upper normal value &amp; Bilirubin&#xD;
             &lt; 2 X upper normal value.&#xD;
&#xD;
         13. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥&#xD;
             1,500/μL and platelet count ≥ 75,000/μL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient with systemic, non-CNS lymphoma metastatic to the CNS.&#xD;
&#xD;
          2. Patient is concurrently using other approved or investigational antineoplastic agents.&#xD;
&#xD;
          3. Presence of active hepatitis B virus(HBV) infection (HBsAg positive and HBV-DNA≥ 104),&#xD;
             hepatitis C virus(HCV) infection, acquired and congenital immunodeficiency diseases&#xD;
             include but not limited to HIV.&#xD;
&#xD;
          4. Patient is allergic to components of the study drug.&#xD;
&#xD;
          5. Patient has an active concurrent malignancy requiring active therapy.&#xD;
&#xD;
          6. Patient has significant abnormalities on screening electrocardiogram (EKG) and active&#xD;
             and significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
             arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension,&#xD;
             valvular disease, pericarditis, or myocardial infarction within 6 months of screening.&#xD;
&#xD;
          7. Patient is known to have an uncontrolled active systemic infection.&#xD;
&#xD;
          8. Patient has a life-threatening illness, medical condition, or organ system dysfunction&#xD;
             that, in the opinion of the investigator, could compromise the subject's safety or put&#xD;
             the study outcomes at undue risk.&#xD;
&#xD;
          9. Women who are pregnant or nursing (lactating), where pregnancy is defined as a state&#xD;
             of a female after conception until the termination of gestation, confirmed by a&#xD;
             positive plasma human chorionic gonadotropin(hCG) laboratory test of &gt; 5 mIU/mL.&#xD;
&#xD;
         10. The patient is unwell or unable to participate in all required study evaluations and&#xD;
             procedures.&#xD;
&#xD;
         11. Drug abuse, medical, psychological or social conditions which may interfering with&#xD;
             subjects' participation in the study or evaluation of the results.&#xD;
&#xD;
         12. Patients considered unsuitable to participate in the study by the researchers.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Xianggui Yuan, MD,PhD</last_name>
    <phone>+8613989883884</phone>
    <email>yuanxg@zju.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Wenbin Qian, MD,PhD</last_name>
    <phone>+8613605801032</phone>
    <email>qianwb@zju.edu.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>2nd Affiliated Hospital, School of Medicine, Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310009</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xianggui Yuan, MD, PhD</last_name>
      <phone>+8613989883884</phone>
      <email>yuanxg@zju.edu.cn</email>
    </contact>
    <contact_backup>
      <last_name>Wenbin Qian, MD, PhD</last_name>
      <phone>+8613605801032</phone>
      <email>qianwb@zju.edu.cn</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>November 6, 2022</last_update_submitted>
  <last_update_submitted_qc>November 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PCNSL</keyword>
  <keyword>Lenalidomide</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Lenalidomide</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/NCT04481815
org study id: IR2020001238
nct id: NCT04481815
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
It is a multicenter, open-Label, randomised phase 2 study to compare the efficacy and safety
      study of R2-MTX chemotherapy（Lenalidomide, Rituximab and Methotrexate）with R-MTX
      chemotherapy（Rituximab and Methotrexate ）as first-line regimens in the treatment of newly
      diagnosed primary central nervous system lymphoma.2-year Progression free survival (PFS) is
      the primary endpoint.
This is a multicenter, open-Label, randomised phase 2 study designed to evaluate the efficacy
      and safety of rituximab plus methotrexate with or without lenalidomide as first-line regimens
      in the treatment of primary central nervous system lymphoma. A total of 240 patients plan to
      participate in this study to receive a total 6 cycles of induction chemotherapy followed by 4
      cycles of maintenance chemotherapy. Follow-ups should be taken up to the first 3 years.The
      primary endpoints were 2-year PFS rate and and secondary endpoints including objective
      response rate (ORR), PFS, overall survival (OS), and adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 2-year progression free survival
time frame: 2 years
description: From date of patients sign informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
measure: Objective response rate
time frame: At the end of Cycle 6 chemotheray
description: At the end of Cycle 6 (each cycle is 21 days) the ratio of numbers of patients with complete response and partial response to all the participants receiving treatment
measure: Overall survival
time frame: 3 years
description: From date of patients sign informed consent until the date of death or the date of last follow-up time, whichever came first, assessed up to 3 years
measure: Progression free survival
time frame: 3 years
description: From date of patients sign informed consent until the date of progression or death or the date of last follow-up time, whichever came first, assessed up to 3 years
measure: Treatment-related adverse events
time frame: 1 year
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: Serum ctDNA biomarkers and tissue biomarkers
time frame: Up to 3 years
description: Next generation sequencing of serum and tissue samples to identify circulating tumor DNA（ctDNA）and tissue biomarkers before and after treatment
arm group label: R2-MTX
arm group type: Experimental
description: Experimental arm will be treated with R2-MTX regimen(Lenalidomide plus Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved complete remission（CR）or partial remission（PR）with additional whole-brain radiotherapy（WBRT）, they processed to R2 maintenance(Lenalidomide plus Rituximab) for 4 cycles.
arm group label: R-MTX
arm group type: Sham Comparator
description: Control arm will be treated with R-MTX regimen(Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved CR or PR with additional WBRT, they processed to Lenalidomide maintenance for 4 cycles.
intervention type: Drug
intervention name: Rituximab
description: 375mg/m2 intravenous infusion d1, every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 375mg/m2 intravenous infusion d1, every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy.
arm group label: R-MTX
arm group label: R2-MTX
intervention type: Drug
intervention name: Lenalidomide
description: 25mg orally d1-10 every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 25mg orally d1-14,d29-42 every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy.
arm group label: R2-MTX
intervention type: Drug
intervention name: Methotrexate
description: 3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle, 6 cycles will be prescribed.
arm group label: R-MTX
arm group label: R2-MTX
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Xianggui Yuan, MD,PhD
phone: +8613989883884
email: yuanxg@zju.edu.cn
last name: Wenbin Qian, MD,PhD
phone: +8613605801032
email: qianwb@zju.edu.cn
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Rituximab
mesh term: Methotrexate
mesh term: Lenalidomide
sharing ipd: No