<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/NCT02229682</url>
  </required_header>
  <id_info>
    <org_study_id>SYSUCC-NKTRT-01</org_study_id>
    <nct_id>NCT02229682</nct_id>
  </id_info>
  <brief_title>Mild-dose IMRT for Early-staged Extranodal Nasal-type NK/T-cell Lymphoma With CR Tumor After GELOX Chemotherapy</brief_title>
  <official_title>Mild-dose Intensity-modulated Radiation Treatment for Stage IE/IIE Extranodal Nasal-type NK/T-cell Lymphoma With Complete Remission Tumor After Combination of Gemcitabine, Oxaliplatin, and Asparaginase (GELOX) Chemotherapy:a Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to make sure whether reduced-dose radiation treatment is sufficient to control&#xD;
      the disease in patients with early-staged extranodal nasal-type NK/T-cell lymphoma, who have&#xD;
      got complete remission tumor after chemotherapy in a new and more effective&#xD;
      asparaginase-based GELOX regimen&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Definitive radiotherapy(RT) is mainstay in combined-modality treatment for patients with&#xD;
      early-staged extranodal nasal-type NK/T-cell lymphoma(ENKTL),it can be used upfront or after&#xD;
      short courses of chemotherapy. The typical dose of RT is recommended as 50-56Gy in&#xD;
      conventional fractionations with 3 dimensional conformal RT or intensity-modulated radiation&#xD;
      treatment(IMRT). Asparaginase-based chemotherapy regimens are being investigated, and primary&#xD;
      results showed superior to previous anthracycline-based (eg. CHOP) chemotherapy. GELOX is a&#xD;
      new asparaginase-based chemotherapy regimen designed and published in our institute, and the&#xD;
      rate of complete remission(CR) is well improved. We hypothesis the reduced-dose radiation&#xD;
      treatment(IMRT in 46Gy) is sufficient to control the disease in patients with early-staged&#xD;
      ENKTL, who have got CR after GELOX chemotherapy, and to validate in this phase II study.&#xD;
&#xD;
        1. Patients:&#xD;
&#xD;
             -  All patients should sign a written informed consent form before enrollment, and the&#xD;
                study should be approved by the Sun Yat-sen University Cancer Center Ethics Board.&#xD;
&#xD;
             -  Baseline of patients: Computed tomography (CT) scans of the chest, abdomen, and&#xD;
                pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone&#xD;
                marrow aspiration or biopsy. Positron emission tomography-CT scans (optional).&#xD;
                Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA).&#xD;
&#xD;
             -  Recheck before and after GELOX chemotherapy and IMRT: Epstein-Barr virus (EBV) DNA&#xD;
                blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), computed tomography (CT)&#xD;
                scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the&#xD;
                head and neck, positron emission tomography-CT scans (optional).&#xD;
&#xD;
        2. Treatment Protocol:&#xD;
&#xD;
             1. The GELOX regimen consist of the following drugs: gemcitabine：1250 mg/ m2 on days&#xD;
                1,iv drip; oxaliplatin：85 mg/m2 on day 1, iv drip; pegaspargase: 2500 IU/m 2 daily&#xD;
                on day 1,intramuscular. The treatment cycle is repeated every 14 days.&#xD;
&#xD;
             2. IMRT is delivered using 6-8MeV linear accelerator using extended involved-field&#xD;
                intensity-modulated radiation treatment planning. The RT dose is 46.2 grays (Gy) in&#xD;
                22 fractions, and a simultaneous-boost method is used.&#xD;
&#xD;
                  -  We assign gross tumor volume (GTV) to 46.2Gy/22F, which is delineated&#xD;
                     according to the initial gross tumor volume identified with imaging and&#xD;
                     physical examination, including the primary tumor and involved regional lymph&#xD;
                     nodes.&#xD;
&#xD;
                  -  The high-risk clinical target volume (CTV1) is assigned to 41.8Gy/22F, which&#xD;
                     is delineated including the first batch of adjacent structures around GTV, and&#xD;
                     lymph node group apt for involvement according to clinical feature of&#xD;
                     individual tumors.&#xD;
&#xD;
                  -  The low-risk clinical target volume (CTV2) is assigned to 36.3Gy/22F, which is&#xD;
                     delineated including the extrapolated structures outside of CTV1 sites, and LN&#xD;
                     groups adjacent to CTV1 LN groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">October 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2016</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>loco-regional tumor control</measure>
    <time_frame>every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years.</time_frame>
    <description>loco-regional tumor control was examined with physical examination and image methods.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>progression-free survival(PFS)</measure>
    <time_frame>every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years</time_frame>
    <description>progression-free survival(PFS): time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival(OS)</measure>
    <time_frame>every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years</time_frame>
    <description>overall survival (OS): time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Lymphoma,</condition>
  <condition>Non-Hodgkin Lymphoma,</condition>
  <condition>Extranodal NK/T-cell Lymphoma,Nasal-type,</condition>
  <arm_group>
    <arm_group_label>Mild-dose IMRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental: Mild-dose of 46Gy with IMRT&#xD;
Drug:&#xD;
gemcitabine：1250mg/m2 (iv drip) on days 1, oxaliplatin: 85 mg/m2 (iv drip) on day 1, and pegaspargase: 2500 IU/m2 (intramuscular injection) on day 1. Cycle is repeated every 14 days&#xD;
IMRT： IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 46.2 grays (Gy) in 22 fractions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Mild-dose IMRT</intervention_name>
    <description>IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 46.2 grays (Gy) in 22 fractions.</description>
    <arm_group_label>Mild-dose IMRT</arm_group_label>
    <other_name>Mild-dose intensity-modulated radiation treatment</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  newly diagnosed ENKTL&#xD;
&#xD;
          -  age:18-75years&#xD;
&#xD;
          -  Ann Arbor stage IE,or stage IIE with cervical lymph node involvement&#xD;
&#xD;
          -  at lease one measurable lesion&#xD;
&#xD;
          -  received GELOX chemotherapy and got CR before radiotherapy&#xD;
&#xD;
          -  Eastern CooperativeOncology Group performance status of 0 to 2&#xD;
&#xD;
          -  Adequate hematologic function (eg, white blood cell ≥ 3×10e9/l,neutrophils count&#xD;
             ≥1.5×10e9/L, and platelet count≥ 100×10e9/L),renal function (eg, serum creatinine≤1.5&#xD;
             mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total&#xD;
             bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase&#xD;
             levels ≤ 3 times the upper limit of normal)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  mismatch the inclusion criteria,&#xD;
&#xD;
          -  got non-CR after GELOX chemotherapy before IMRT,&#xD;
&#xD;
          -  systematic central nervous system involvement, previous or concomitant malignancies&#xD;
             and any coexisting medical problems that could cause poor compliance with the study&#xD;
             protocol,&#xD;
&#xD;
          -  primary lesion not from the upper aerodigestive tract&#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_official>
    <last_name>Yujing Zhang, MD/PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yujing ZHANG, MD/PHD</last_name>
    <phone>86-20-87343702</phone>
    <email>zhangyj@sysucc.org.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Dept. Radiation Oncology, Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Yujing Zhang, MD/PhD</last_name>
      <phone>86-20-87343702</phone>
      <email>zhangyj@sysucc.org.cn</email>
    </contact>
    <investigator>
      <last_name>Yujing Zhang, MD/PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. doi: 10.1002/cncr.27752. Epub 2012 Jul 18.</citation>
    <PMID>22811078</PMID>
  </reference>
  <reference>
    <citation>Gregoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, Lee A, Le QT, Maingon P, Nutting C, O'Sullivan B, Porceddu SV, Lengele B. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014 Jan;110(1):172-81. doi: 10.1016/j.radonc.2013.10.010. Epub 2013 Oct 31.</citation>
    <PMID>24183870</PMID>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>September 28, 2014</last_update_submitted>
  <last_update_submitted_qc>September 28, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 30, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Yujing ZHANG, MD/PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>extranodal NK/T-cell lymphoma,nasal-type,</keyword>
  <keyword>radiotherapy,</keyword>
  <keyword>intensity-modulated radiation treatment,</keyword>
  <keyword>asparaginase-based chemotherapy,</keyword>
  <keyword>loco-regional control,</keyword>
  <keyword>survival</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>
    <mesh_term>Lymphoma, Extranodal NK-T-Cell</mesh_term>
  </condition_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/NCT02229682
org study id: SYSUCC-NKTRT-01
nct id: NCT02229682
lead sponsor: 
has dmc: Yes
This study is to make sure whether reduced-dose radiation treatment is sufficient to control
      the disease in patients with early-staged extranodal nasal-type NK/T-cell lymphoma, who have
      got complete remission tumor after chemotherapy in a new and more effective
      asparaginase-based GELOX regimen
Definitive radiotherapy(RT) is mainstay in combined-modality treatment for patients with
      early-staged extranodal nasal-type NK/T-cell lymphoma(ENKTL),it can be used upfront or after
      short courses of chemotherapy. The typical dose of RT is recommended as 50-56Gy in
      conventional fractionations with 3 dimensional conformal RT or intensity-modulated radiation
      treatment(IMRT). Asparaginase-based chemotherapy regimens are being investigated, and primary
      results showed superior to previous anthracycline-based (eg. CHOP) chemotherapy. GELOX is a
      new asparaginase-based chemotherapy regimen designed and published in our institute, and the
      rate of complete remission(CR) is well improved. We hypothesis the reduced-dose radiation
      treatment(IMRT in 46Gy) is sufficient to control the disease in patients with early-staged
      ENKTL, who have got CR after GELOX chemotherapy, and to validate in this phase II study.

        1. Patients:

             -  All patients should sign a written informed consent form before enrollment, and the
                study should be approved by the Sun Yat-sen University Cancer Center Ethics Board.

             -  Baseline of patients: Computed tomography (CT) scans of the chest, abdomen, and
                pelvis, magnetic resonance imaging studies of the head and neck, and bilateral bone
                marrow aspiration or biopsy. Positron emission tomography-CT scans (optional).
                Epstein-Barr virus (EBV) DNA blood levels, titer of EBV antibody (EA-IgA, VCA-IgA).

             -  Recheck before and after GELOX chemotherapy and IMRT: Epstein-Barr virus (EBV) DNA
                blood levels, titer of EBV antibody (EA-IgA, VCA-IgA), computed tomography (CT)
                scans of the chest, abdomen, and pelvis, magnetic resonance imaging studies of the
                head and neck, positron emission tomography-CT scans (optional).

        2. Treatment Protocol:

             1. The GELOX regimen consist of the following drugs: gemcitabine：1250 mg/ m2 on days
                1,iv drip; oxaliplatin：85 mg/m2 on day 1, iv drip; pegaspargase: 2500 IU/m 2 daily
                on day 1,intramuscular. The treatment cycle is repeated every 14 days.

             2. IMRT is delivered using 6-8MeV linear accelerator using extended involved-field
                intensity-modulated radiation treatment planning. The RT dose is 46.2 grays (Gy) in
                22 fractions, and a simultaneous-boost method is used.

                  -  We assign gross tumor volume (GTV) to 46.2Gy/22F, which is delineated
                     according to the initial gross tumor volume identified with imaging and
                     physical examination, including the primary tumor and involved regional lymph
                     nodes.

                  -  The high-risk clinical target volume (CTV1) is assigned to 41.8Gy/22F, which
                     is delineated including the first batch of adjacent structures around GTV, and
                     lymph node group apt for involvement according to clinical feature of
                     individual tumors.

                  -  The low-risk clinical target volume (CTV2) is assigned to 36.3Gy/22F, which is
                     delineated including the extrapolated structures outside of CTV1 sites, and LN
                     groups adjacent to CTV1 LN groups.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: loco-regional tumor control
time frame: every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years.
description: loco-regional tumor control was examined with physical examination and image methods.
measure: progression-free survival(PFS)
time frame: every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years
description: progression-free survival(PFS): time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first
measure: overall survival(OS)
time frame: every 3 months after IMRT for 2 years, and then every 6 months for the next 3 years
description: overall survival (OS): time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first.
arm group label: Mild-dose IMRT
arm group type: Experimental
description: Experimental: Mild-dose of 46Gy with IMRT
Drug:
gemcitabine：1250mg/m2 (iv drip) on days 1, oxaliplatin: 85 mg/m2 (iv drip) on day 1, and pegaspargase: 2500 IU/m2 (intramuscular injection) on day 1. Cycle is repeated every 14 days
IMRT： IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 46.2 grays (Gy) in 22 fractions.
intervention type: Radiation
intervention name: Mild-dose IMRT
description: IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 46.2 grays (Gy) in 22 fractions.
arm group label: Mild-dose IMRT
other name: Mild-dose intensity-modulated radiation treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yujing Zhang, MD/PhD
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: Yujing ZHANG, MD/PHD
phone: 86-20-87343702
email: zhangyj@sysucc.org.cn
facility: 
contact: 
investigator: 
country: China
citation: Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. doi: 10.1002/cncr.27752. Epub 2012 Jul 18.
PMID: 22811078
citation: Gregoire V, Ang K, Budach W, Grau C, Hamoir M, Langendijk JA, Lee A, Le QT, Maingon P, Nutting C, O'Sullivan B, Porceddu SV, Lengele B. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014 Jan;110(1):172-81. doi: 10.1016/j.radonc.2013.10.010. Epub 2013 Oct 31.
PMID: 24183870
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Yujing ZHANG, MD/PhD
investigator title: Professor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral
mesh term: Lymphoma, Extranodal NK-T-Cell