<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/NCT03293173</url>
  </required_header>
  <id_info>
    <org_study_id>NLG-LBC-06</org_study_id>
    <nct_id>NCT03293173</nct_id>
  </id_info>
  <brief_title>Biomarker Driven Intensified ChemoImmunotherapy With Early CNS Prophylaxis</brief_title>
  <acronym>Bio-CHIC</acronym>
  <official_title>Biomarker Driven and Dose Intensified Chemoimmunotherapy With Early CNS Prophylaxis in Patients Less Than 65 Years With High Risk Diffuse Large B-Cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nordic Lymphoma Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Helsinki University Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nordic Lymphoma Group</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 study is testing whether stratification of the patients according to biological risk&#xD;
      factors for different treatment groups will improve the outcome of patients with clinically&#xD;
      high diffuse large B-cell lymphoma (DLBCL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For young clinically high-risk diffuse large B-cell lymphoma (DLBCL) patients the optimal&#xD;
      therapy has not been established. Previous Nordic phase II studies, where dose-dense&#xD;
      chemoimmunotherapy (R-CHOEP-14) with systemic CNS prophylaxis (HD-Mtx and HD-AraC) was given,&#xD;
      demonstrated favorable outcome in comparison to historical controls. However, the patients&#xD;
      with biological risk factors, such as translocation of bcl2 and myc oncogenes or and/or high&#xD;
      BCL2 and MYC expression or deletion 17p and/or high P53 expression had significantly higher&#xD;
      risk of death, as compared to patients without aberrations. The figures provide evidence for&#xD;
      an unmet clinical need for the patients with biological risk factors, and underscore the&#xD;
      importance of a clinical trial, where both biological and clinical risk factors play a role&#xD;
      in the treatment planning.&#xD;
&#xD;
      In this trial treatment intensity varies according to presence or absence of biological risk&#xD;
      factors. All patients receive a prephase medication consisting of prednisone and vincristine&#xD;
      and two cycles of R-CHOP and high dose (HD) methotrexate. Subsequently, depending on the&#xD;
      biological risk factors either four additional cycles of R-CHOEP (standard arm with no risk&#xD;
      factors) or four dose adjusted R-EPOCH courses (experimental arm with risk factors) are&#xD;
      given, followed by one course of high dose cytarabine (Ara-C) and R. R-CHOEP courses should&#xD;
      be given with a two-week and R-EPOCH with a three-week interval.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 4, 2017</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Stratification into group A (standard) or group B (experimental) based on biological risk factors</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to treatment failure (TTF) of the patients with biological risk factors</measure>
    <time_frame>At 3 years</time_frame>
    <description>Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure (TTF) at 3 years from date of registration of all patients and the patients in the low risk group</measure>
    <time_frame>At 3 years</time_frame>
    <description>Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events (Safety and tolerability)</measure>
    <time_frame>During the treatment period at the end of each cycle (14 or 21 days) up to 6 months. In addition, severe late toxicities during follow-up at 6 months intervals through study completion, an average of 5.5 years.</time_frame>
    <description>Number of patients with treatment-related adverse events graded according to the NCI CTCAE v 4.03</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical response rate of all patients and the patients with biological risk factors</measure>
    <time_frame>At the end of treatment cycles 2 and 7. Each cycle is two (group A) or three weeks (group B)</time_frame>
    <description>Number of patients with complete or partial response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CNS relapse rate</measure>
    <time_frame>At 1,5 years</time_frame>
    <description>Number of patients with CNS progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival rate (PFS) of all patients and the patients with biological risk factors</measure>
    <time_frame>At 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival rate (OS) of all patients and the patients with biological risk factors</measure>
    <time_frame>At 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Molecular correlates for survival</measure>
    <time_frame>At 3 years</time_frame>
    <description>Identification of genomic aberrations (for example mutations and translocations), gene expression profiles and protein expression from the tumor tissue and circulation that predict clinical course of the disease</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Lymphoma, Large B-Cell, Diffuse</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Biologically low risk group, R-CHOEP-14</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Biologically high risk group, DA-EPOCH-R</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>R-CHOEP</intervention_name>
    <description>rituximab, cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone</description>
    <arm_group_label>Group A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>DA-EPOCH-R</intervention_name>
    <description>dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab</description>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 - 64 years&#xD;
&#xD;
          -  Histologically confirmed CD20+ DLBCL based on revised WHO 2008 Lymphoma&#xD;
             Classification. The following subgroups and variants can be included:&#xD;
&#xD;
               -  ALK-positive large B-cell lymphoma&#xD;
&#xD;
               -  Intravascular large B-cell lymphoma&#xD;
&#xD;
               -  T-cell rich B-cell lymphoma&#xD;
&#xD;
               -  Myc/BCL-2 double hit lymphoma&#xD;
&#xD;
               -  Follicular lymphomas grade 3b&#xD;
&#xD;
               -  DLBCL with previously undiagnosed concurrent small cell infiltration in bone&#xD;
                  marrow, lymph node, or extranodal site and lymphomas intermediate between DLBCL&#xD;
                  and Burkitt's lymphoma are allowed&#xD;
&#xD;
               -  Posttransplantation lymphoma (PTLD), discordant or transformed lymphoma are NOT&#xD;
                  allowed&#xD;
&#xD;
          -  Patients in at least stage II with age adjusted IPI score of 2 or 3:&#xD;
&#xD;
               -  Stage III /IV and elevated LDH&#xD;
&#xD;
               -  Stage III/IV and WHO performance status 2 - 3&#xD;
&#xD;
               -  Stage II and elevated LDH and WHO performance status 2 - 3&#xD;
&#xD;
          -  And/or patients with site specific risk factors for CNS recurrence defined as follows&#xD;
&#xD;
               -  More than one extranodal site&#xD;
&#xD;
               -  Testicular lymphoma, stage IIE and higher&#xD;
&#xD;
               -  Paranasal sinus and orbital lymphoma with destruction of bone&#xD;
&#xD;
               -  Large cell lymphoma infiltration of the bone marrow&#xD;
&#xD;
          -  Previously untreated, except steroids allowed&#xD;
&#xD;
          -  WHO performance status 0-3&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe cardiac disease: cardiac function grade 3-4, left ventricular ejection fraction&#xD;
             &lt;45%&#xD;
&#xD;
          -  Impaired bone marrow liver, renal or other organ function not caused by lymphoma,&#xD;
             which will interfere with the treatment schedule (Hemoglobin &lt; 9 g/dL, ANC &lt; 1.5 ×&#xD;
             109/L, Platelet count &lt; 75 × 109/L, creatinine clearance &lt; 40 mL/min, ALT/AST &gt; 2.5 x&#xD;
             ULN, bilirubin 1.5 x ULN, INR &gt; 1.5)&#xD;
&#xD;
          -  Pregnancy/lactation&#xD;
&#xD;
          -  Men and women of reproductive potential not agreeing to use effective contraception&#xD;
             during treatment and for 18 months after completion of treatment (Effective&#xD;
             contraception is combined (estrogen and progestogen containing) hormonal contraception&#xD;
             associated with inhibition of ovulation (oral, intravaginal or transdermal),&#xD;
             progestogen-only hormonal contraception associated with inhibition of ovulation (oral,&#xD;
             injectable or implantable), intrauterine device (IUD), hormone-releasing IUD,&#xD;
             bilateral tubal occlusion, vasectomised partner, or sexual abstinence&#xD;
&#xD;
          -  Patients with other severe medical problems, including active infections, cardiac or&#xD;
             pulmonary disease, history of PML and with an expected short survival for non-lymphoma&#xD;
             reasons&#xD;
&#xD;
          -  Known HIV positivity&#xD;
&#xD;
          -  Active or chronic hepatitis B virus (HBV) infection (defined as positive HBsAg&#xD;
             serology), or active hepatitis C virus (HCV) infection (defined by antibody serology&#xD;
             testing). HBsAg, HBcAb, and HCVAb must be tested during screening. Patients who have&#xD;
             protective titers of HBsAb along negative HBsAg after vaccination or prior but cured&#xD;
             hepatitis B are eligible.&#xD;
&#xD;
          -  Vaccination with a live vaccine within one month prior to randomization&#xD;
&#xD;
          -  Patients with a malignancy that has been treated but not with curative intent, unless&#xD;
             the malignancy has been in remission without treatment for ≥ 5 years prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Earlier treatment containing anthracyclines&#xD;
&#xD;
          -  Psychiatric or mental disorder which make the patient unable to give an informed&#xD;
             consent and/or adhere to the protocol&#xD;
&#xD;
          -  CNS disease as diagnosed by MRI or CSF cytology. Positive CSF flow cytometry below&#xD;
             diagnostic threshold level by cytology is allowed&#xD;
&#xD;
          -  Transformed lymphoma&#xD;
&#xD;
          -  Primary mediastinal B-cell lymphoma&#xD;
&#xD;
          -  Pleural or peritoneal fluid that cannot be drained safely&#xD;
&#xD;
          -  Hypersensitivity to the active substance or any of the other ingredients&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal&#xD;
             antibodies or known sensitivity or allergy to murine products&#xD;
&#xD;
          -  Patients participating in other clinical studies, unless followed for survival&#xD;
&#xD;
          -  Lower urinary tract constriction, which cannot be treated adequately&#xD;
&#xD;
          -  Degenerative and toxic encephalopathy&#xD;
&#xD;
          -  Neuromuscular disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sirpa Leppa, prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Helsinki University Hospital Cancer Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laura K Hakala</last_name>
    <phone>+358503729043</phone>
    <email>ext-laura.k.hakala@hus.fi</email>
  </overall_contact>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Judit Joergensen, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Judit Joergensen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept of Haematology, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Brown, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Peter Brown</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept of Haematology, Herlev Hospital, Copenhagen</name>
      <address>
        <city>Herlev</city>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Danny Stoltenberg, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Danny Stoltenberg</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept haematology, Odense University hospital</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Stauffer Larsen, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Thomas Stauffer Larsen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept of Haematology, Sjaellands University hospital, Roskilde</name>
      <address>
        <city>Roskilde</city>
        <zip>4000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christian Bjorn Poulsen, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Christian Bjorn Poulsen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Helsinki University Hospital Cancer Centre</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laura K Hakala</last_name>
      <phone>+358503729043</phone>
      <email>ext-laura.k.hakala@hus.fi</email>
    </contact>
    <investigator>
      <last_name>Sirpa Leppä, prof</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Keski-Suomen keskussairaala</name>
      <address>
        <city>Jyväskylä</city>
        <zip>40620</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kaija Vasala, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Kaija Vasala</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kuopio University Hospital</name>
      <address>
        <city>Kuopio</city>
        <zip>70029</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Annikki Aromaa-Häyhä, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Annikki Aromaa-Häyhä</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>TAYS</name>
      <address>
        <city>Tampere</city>
        <zip>33521</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kaisa Sunela, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Kaisa Sunela</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Turku University Hospital, Syöpäklinikka</name>
      <address>
        <city>Turku</city>
        <zip>20520</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sirkku Jyrkkiö, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Sirkku Jyrkkiö</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept. of Oncology, Helse Bergen HF Haukeland sykehus</name>
      <address>
        <city>Bergen</city>
        <zip>5021</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Oystein Fluge, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Oystein Fluge</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Harald Holte, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Harald Holte</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept. of Haematology and Oncology, Helse Stavander HF sykehuset</name>
      <address>
        <city>Stavanger</city>
        <zip>4011</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Meyer, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Peter Meyer</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept. of Oncology, Universitetssykehuset i Nord-Norge HF</name>
      <address>
        <city>Tromsø</city>
        <zip>9038</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin Maisenhölder, Md, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Martin Maisenhölder</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dept of Oncology, St. Olavs hospital HF</name>
      <address>
        <city>Trondheim</city>
        <zip>7006</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Unn Merete Fagerli, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Unn Merete Fagerli</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Skåne University Hospital</name>
      <address>
        <city>Lund</city>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristina Drott, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Kristina Drott</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <reference>
    <citation>Fiskvik I, Beiske K, Delabie J, Yri O, Spetalen S, Karjalainen-Lindsberg ML, Leppa S, Liestol K, Smeland EB, Holte H. Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1742-9. doi: 10.3109/10428194.2014.970550. Epub 2014 Nov 19.</citation>
    <PMID>25284491</PMID>
  </reference>
  <reference>
    <citation>Holte H, Leppa S, Bjorkholm M, Fluge O, Jyrkkio S, Delabie J, Sundstrom C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fossa A, Ostenstad B, Lofvenberg E, Nordstrom M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. doi: 10.1093/annonc/mds621. Epub 2012 Dec 17.</citation>
    <PMID>23247661</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>March 3, 2020</last_update_submitted>
  <last_update_submitted_qc>March 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DLBCL</keyword>
  <keyword>Chemoimmunotherapy</keyword>
  <keyword>High risk</keyword>
  <keyword>CNS prophylaxis</keyword>
  <keyword>Biomarker-driven</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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>individual deidentified participant data (including data dictionaries) will be shared</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Beginning 3 months and ending 5 years following article publication</ipd_time_frame>
    <ipd_access_criteria>Researchers who provide a methodologically sound proposal.</ipd_access_criteria>
  </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/NCT03293173
org study id: NLG-LBC-06
nct id: NCT03293173
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is testing whether stratification of the patients according to biological risk
      factors for different treatment groups will improve the outcome of patients with clinically
      high diffuse large B-cell lymphoma (DLBCL).
For young clinically high-risk diffuse large B-cell lymphoma (DLBCL) patients the optimal
      therapy has not been established. Previous Nordic phase II studies, where dose-dense
      chemoimmunotherapy (R-CHOEP-14) with systemic CNS prophylaxis (HD-Mtx and HD-AraC) was given,
      demonstrated favorable outcome in comparison to historical controls. However, the patients
      with biological risk factors, such as translocation of bcl2 and myc oncogenes or and/or high
      BCL2 and MYC expression or deletion 17p and/or high P53 expression had significantly higher
      risk of death, as compared to patients without aberrations. The figures provide evidence for
      an unmet clinical need for the patients with biological risk factors, and underscore the
      importance of a clinical trial, where both biological and clinical risk factors play a role
      in the treatment planning.

      In this trial treatment intensity varies according to presence or absence of biological risk
      factors. All patients receive a prephase medication consisting of prednisone and vincristine
      and two cycles of R-CHOP and high dose (HD) methotrexate. Subsequently, depending on the
      biological risk factors either four additional cycles of R-CHOEP (standard arm with no risk
      factors) or four dose adjusted R-EPOCH courses (experimental arm with risk factors) are
      given, followed by one course of high dose cytarabine (Ara-C) and R. R-CHOEP courses should
      be given with a two-week and R-EPOCH with a three-week interval.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Stratification into group A (standard) or group B (experimental) based on biological risk factors
primary purpose: Treatment
masking: None (Open Label)
measure: Time to treatment failure (TTF) of the patients with biological risk factors
time frame: At 3 years
description: Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.
measure: Time to treatment failure (TTF) at 3 years from date of registration of all patients and the patients in the low risk group
time frame: At 3 years
description: Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.
measure: Incidence of treatment-emergent adverse events (Safety and tolerability)
time frame: During the treatment period at the end of each cycle (14 or 21 days) up to 6 months. In addition, severe late toxicities during follow-up at 6 months intervals through study completion, an average of 5.5 years.
description: Number of patients with treatment-related adverse events graded according to the NCI CTCAE v 4.03
measure: Clinical response rate of all patients and the patients with biological risk factors
time frame: At the end of treatment cycles 2 and 7. Each cycle is two (group A) or three weeks (group B)
description: Number of patients with complete or partial response
measure: CNS relapse rate
time frame: At 1,5 years
description: Number of patients with CNS progression
measure: Progression free survival rate (PFS) of all patients and the patients with biological risk factors
time frame: At 3 years
measure: Overall survival rate (OS) of all patients and the patients with biological risk factors
time frame: At 3 years
measure: Molecular correlates for survival
time frame: At 3 years
description: Identification of genomic aberrations (for example mutations and translocations), gene expression profiles and protein expression from the tumor tissue and circulation that predict clinical course of the disease
arm group label: Group A
arm group type: Experimental
description: Biologically low risk group, R-CHOEP-14
arm group label: Group B
arm group type: Experimental
description: Biologically high risk group, DA-EPOCH-R
intervention type: Combination Product
intervention name: R-CHOEP
description: rituximab, cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone
arm group label: Group A
intervention type: Combination Product
intervention name: DA-EPOCH-R
description: dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Sirpa Leppa, prof
role: Principal Investigator
affiliation: Helsinki University Hospital Cancer Centre
last name: Laura K Hakala
phone: +358503729043
email: ext-laura.k.hakala@hus.fi
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status: Recruiting
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country: Denmark
country: Finland
country: Norway
country: Sweden
citation: Fiskvik I, Beiske K, Delabie J, Yri O, Spetalen S, Karjalainen-Lindsberg ML, Leppa S, Liestol K, Smeland EB, Holte H. Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1742-9. doi: 10.3109/10428194.2014.970550. Epub 2014 Nov 19.
PMID: 25284491
citation: Holte H, Leppa S, Bjorkholm M, Fluge O, Jyrkkio S, Delabie J, Sundstrom C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fossa A, Ostenstad B, Lofvenberg E, Nordstrom M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. doi: 10.1093/annonc/mds621. Epub 2012 Dec 17.
PMID: 23247661
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Large B-Cell, Diffuse
sharing ipd: Yes
ipd description: individual deidentified participant data (including data dictionaries) will be shared
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Beginning 3 months and ending 5 years following article publication
ipd access criteria: Researchers who provide a methodologically sound proposal.