<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/NCT04442412</url>
  </required_header>
  <id_info>
    <org_study_id>FIL_PREVID</org_study_id>
    <nct_id>NCT04442412</nct_id>
  </id_info>
  <brief_title>Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy</brief_title>
  <acronym>FIL_PREVID</acronym>
  <official_title>Prephase Treatment With Prednisone +/- Vitamin D Supplementation Followed by Immunochemotherapy in Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL) A Randomized, Open Label, Phase III Study by Fondazione Italiana Linfomi.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione Italiana Linfomi - ETS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GRADE Onlus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fondazione Italiana Linfomi - ETS</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is an open-label, multicenter, randomized phase III trial. The study plans to randomize&#xD;
      patients with a 1 to 1 ratio to Arm A (Standard arm) or Arm B (Experimental arm).&#xD;
&#xD;
      All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of&#xD;
      immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental&#xD;
      arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD&#xD;
      during the intere period of immunochemotherapy according to a prefixed schedule. Choice of&#xD;
      type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment result, but&#xD;
      treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After the patient signs the written informed consent the patient will enter the screening&#xD;
      phase planning baseline assessments and will be randomly allocated with a 1 to 1 ratio to Arm&#xD;
      A (Standard arm) or Arm B (Experimental arm).&#xD;
&#xD;
      Patients randomized to Arm A will receive a prephase with oral prednisone (50 mg for 7 days&#xD;
      [day -6 to day 0]) followed by 6 courses of R-CHOP or R-miniCHOP every 21 days.&#xD;
&#xD;
      If patients randomized to arm A are already on VitD, they are allowed to continue receiving&#xD;
      VitD supplementation at a dose that can be considered part of the standard of care and does&#xD;
      not exceed the maximum standard VitD dose recommended for general adult and elderly&#xD;
      population , up to 10,000 U/week VitD .&#xD;
&#xD;
      If clinically indicated at treating physician judgement, patients could receive 1 mg of&#xD;
      vincristine on the first day of prephase ; in this case vincristine administration in cycle 1&#xD;
      of immunochemotherapy should be skipped, in patients receiving R-miniCHOP; reduced to 1 mg,&#xD;
      in patients receiving R-CHOP.&#xD;
&#xD;
      Patients randomized to Arm B will receive a prephase with oral prednisone and a prephase&#xD;
      therapy with VitD according to the below reported schedule followed by 6 courses of R-CHOP or&#xD;
      R-miniCHOP every 21 days.&#xD;
&#xD;
      Schedule for VitD (Cholecalciferol) supplementation: 25,000 U/day starting on day -6:&#xD;
&#xD;
      daily loading dose for 7 days if 25 VitD baseline level 20-40 ng/ml daily loading dose for 14&#xD;
      days if 25 VitD baseline level &lt; 20 ng/ml followed by weekly maintenance supplementation of&#xD;
      25,000 U for the entire duration of immunochemotherapy (6 courses every 21 days - 18 weeks),&#xD;
      regardless of the baseline level of 25 VitD.&#xD;
&#xD;
      If clinically indicated at treating physician judgement, patients could receive 1 mg of&#xD;
      vincristine on the first day of prephase (DAY -6); in this case vincristine administration in&#xD;
      cycle 1 of immunochemotherapy should be: skipped, in patients receiving R-miniCHOP; reduced&#xD;
      to 1 mg, in patients receiving R-CHOP.&#xD;
&#xD;
      Patients with 25(OH)VitD levels &lt;30 ng/ml on d1 cycle 2 will receive and additional loading&#xD;
      phase of Cholecalciferol 25,000 U/day for 7 days and then 25,000 U once weekly for the&#xD;
      duration of immunochemotherapy.&#xD;
&#xD;
      Patients may continue with VitD supplementation after the end of the immunochemotherapy at a&#xD;
      (reduced) standard dose of 25,000 U once a month for up to 2 years from end of&#xD;
      immunochemotherapy.&#xD;
&#xD;
      Patients experimenting toxicity leading to a delay in treatment administration &gt; 4 weeks will&#xD;
      discontinue study treatment and will be addressed to a salvage treatment: these patients will&#xD;
      be followed-up for survival until the end of the study.&#xD;
&#xD;
      Consolidation radiotherapy:&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 23, 2021</start_date>
  <completion_date type="Anticipated">September 1, 2030</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2025</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>
    <intervention_model_description>This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1 to 1 ratio to Arm A (Standard arm) or Arm B (Experimental arm). All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>at the end of treatment - 54 months</time_frame>
    <description>Progression-Free Survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>at the end of treatment - 54 months</time_frame>
    <description>Overall Survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event Free Survival</measure>
    <time_frame>at the end of treatment - 54 months</time_frame>
    <description>Event Free Survival (EFS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>at the end of treatment - 54 months</time_frame>
    <description>Response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Early death rate</measure>
    <time_frame>at the end of treatment - 54 months</time_frame>
    <description>Early death rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of ECOG changes after prephase</measure>
    <time_frame>at the end of treatment - 54 months</time_frame>
    <description>Rate of ECOG changes after prephase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of patients who maintain 25(OH)VitD levels</measure>
    <time_frame>At the beginning of Cycle 2 (each cycle is 21 days)</time_frame>
    <description>Rate of patients who maintain 25(OH)VitD levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of 25(OH)VitD correction (VitD supplementation arm)</measure>
    <time_frame>At the beginning of Cycle 2 (each cycle is 21 days)</time_frame>
    <description>Rate of 25(OH)VitD correction (VitD supplementation arm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time-to-deterioration physical functioning and fatigue</measure>
    <time_frame>At the beginning of Cycle 2 (each cycle is 21 days)</time_frame>
    <description>time-to-deterioration physical functioning and fatigue</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">430</enrollment>
  <condition>Diffuse Large B-Cell Lymphoma</condition>
  <condition>Elderly Patients</condition>
  <arm_group>
    <arm_group_label>Arm B (Experimental):</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to Arm B will receive a prephase with oral prednisone and a prephase therapy with VitD according to the below reported schedule followed by 6 courses of R-CHOP or R-miniCHOP every 21 days.&#xD;
Schedule for VitD supplementation: 25,000 U/day starting on day -6:&#xD;
daily loading dose for 7 days if 25 VitD baseline level 20-40 ng/ml daily loading dose for 14 days if 25 VitD baseline level &lt; 20 ng/ml followed by weekly maintenance supplementation of 25,000 U for the entire duration of immunochemotherapy (6 courses every 21 days - 18 weeks), regardless of the baseline level of 25 VitD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm A (Standard arm)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients randomized to Arm A will receive a prephase with oral prednisone followed by 6 courses of R-CHOP or R-miniCHOP every 21 days.&#xD;
If patients randomized to arm A are already on VitD, they are allowed to continue receiving VitD supplementation at a dose that can be considered part of the standard of care and does not exceed the maximum standard VitD dose recommended for general adult and elderly population , up to 10,000 U/week VitD</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3 (Cholecalciferol)</intervention_name>
    <description>patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment (CGA) result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.</description>
    <arm_group_label>Arm B (Experimental):</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RCHOP o R-miniCHOP at standard doses</intervention_name>
    <description>Patients on both arms receive pre-treatment with prednisone oral before 6 cycles of 21 days each of immunochemotherapy with RCHOP&#xD;
o R-miniCHOP at standard doses</description>
    <arm_group_label>Arm A (Standard arm)</arm_group_label>
    <arm_group_label>Arm B (Experimental):</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          1. Histologically documented diagnosis of Diffuse Large B-cell Lymphoma or Follicular&#xD;
             grade IIIb lymphoma, as defined in the 2017 edition of the World Health Organization&#xD;
             (WHO) classification.&#xD;
&#xD;
          2. Age ≥ 65 years&#xD;
&#xD;
          3. Comprehensive Geriatric Assessment performed at baseline, before start of any&#xD;
             treatment.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group performance status (PS) ≤3&#xD;
&#xD;
          5. Eligibility for anthracycline containing regimen (R-CHOP or R-miniCHOP)&#xD;
&#xD;
          6. No previous treatment for DLBCL or Follicular grade IIIb lymphoma&#xD;
&#xD;
          7. Ann Arbor stage I-IV&#xD;
&#xD;
          8. At least one site of measurable nodal disease at baseline ≥ 1.5 cm in the longest&#xD;
             transverse diameter as determined by CT scan ; or one metabolic active site of disease&#xD;
             at baseline FDG-PET scan&#xD;
&#xD;
          9. Serum basic levels of Vitamin D [25 (OH) VitD] ≤ 40 ng / ml;&#xD;
&#xD;
         10. Adequate hematological counts defined as follows:&#xD;
&#xD;
               -  Absolute Neutrophil count &gt; 1.5 x 109/L unless due to bone marrow involvement by&#xD;
                  lymphoma&#xD;
&#xD;
               -  Platelet count ≥ 80.000/mm3 unless due to bone marrow involvement by lymphoma&#xD;
&#xD;
         11. Adequate renal function defined as follows:&#xD;
&#xD;
             - Creatinine ≤ 2 mg/dL, unless secondary to lymphoma&#xD;
&#xD;
         12. Adequate hepatic function defined as follows:&#xD;
&#xD;
             - Bilirubin ≤ 2 mg/dL unless secondary to lymphoma&#xD;
&#xD;
         13. LVEF &gt; 50% at bidimensionally echocardiogram&#xD;
&#xD;
         14. Life expectancy ≥ 6 months&#xD;
&#xD;
         15. Subject understands and voluntarily signs an informed consent form approved by an&#xD;
             Independent Ethics Committee , prior to the initiation of any screening or&#xD;
             study-specific procedures&#xD;
&#xD;
         16. Subject must be able to adhere to the study visit schedule and other protocol&#xD;
             requirements&#xD;
&#xD;
         17. Men must agree to use one of the below reported acceptable method of contraception for&#xD;
             the duration of the study and for 3 months after receiving the last dose of&#xD;
             immunochemotherapy, and to not donate sperm while on study.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Histological diagnosis different from Diffuse large B-Cell Lymphoma or Follicular&#xD;
             grade IIIb lymphoma, including diagnosis of HGBL, with rearrangement of MYC, BCL2&#xD;
             and/or BCL6 (double-hit)&#xD;
&#xD;
          2. Use of VitD supplementation as standard of care at dose higher than 10,000 U/week&#xD;
&#xD;
          3. Suspect or clinical evidence of CNS involvement by lymphoma&#xD;
&#xD;
          4. Contraindication to the use of rituximab&#xD;
&#xD;
          5. Contraindication to the use of VitD supplementation (Hypercalcemia/Hyperphosphatemia)&#xD;
&#xD;
          6. Subject has received any anti-cancer therapy including chemotherapy, immunotherapy,&#xD;
             radiotherapy, investigational therapy, including targeted small molecule agents within&#xD;
             14 days prior to the first dose of study drug&#xD;
&#xD;
          7. Significant history of neurologic, psychiatric, endocrinological, metabolic,&#xD;
             immunologic, or hepatic disease that would preclude participation in the study or&#xD;
             compromise ability to give informed consent&#xD;
&#xD;
          8. Any history of other active malignancies within 2 years prior to study entry, with the&#xD;
             exception of adequately treated in situ carcinoma of the cervix uterine, basal cell&#xD;
             carcinoma of the skin or localized squamous cell carcinoma of the skin or limited&#xD;
             stage surgically removed breast cancer or adequately treated with radiation therapy or&#xD;
             limited stage prostate carcinoma surgically removed or adequately treated with&#xD;
             radiation therapy or previous malignancy confined and surgically resected with&#xD;
             curative intent&#xD;
&#xD;
          9. Evidence of other clinically significant uncontrolled condition including, but not&#xD;
             limited to:&#xD;
&#xD;
               -  Uncontrolled and/or active systemic infection (viral, bacterial or fungal)&#xD;
&#xD;
               -  Chronic hepatitis B virus or hepatitis C requiring treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesco Merli, Dott.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Reggio Emilia - Azienda Unitа Sanitaria Locale-IRCCS</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lorenza Randi, Dott.ssa</last_name>
    <phone>0000000000</phone>
    <email>lrandi@filinf.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Francesco Merli, Dott.</last_name>
    <phone>0000000000</phone>
    <email>startup@filinf.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>SC Ematologia Spedali Civili</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandra Tucci</last_name>
      <email>alessandra.tucci@ospedalicivili.brescia.it</email>
    </contact>
    <investigator>
      <last_name>Alessandra Tucci, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UO Ematologia e CTMO di Piacenza</name>
      <address>
        <city>Piacenza</city>
        <state>PC</state>
        <zip>29121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Annalisa Arcari, MD</last_name>
      <email>a.arcari@ausl.pc.it</email>
    </contact>
    <investigator>
      <last_name>Annalisa Arcari, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ospedale Oncologico regionale CROB</name>
      <address>
        <city>Rionero in Vulture</city>
        <state>Piacenza</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giuseppe Pietrantuono, MD</last_name>
      <email>ematologia45@alice.it</email>
    </contact>
    <investigator>
      <last_name>Giuseppe Pietrantuono, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia</name>
      <address>
        <city>Alessandria</city>
        <zip>15121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuela Zanni, MD</last_name>
      <email>manuela.zanni@ospedale.al.it</email>
    </contact>
    <contact_backup>
      <last_name>Maria Vittoria Sacchi</last_name>
      <email>mariavittoria.sacchi@ospedale.al.it</email>
    </contact_backup>
    <investigator>
      <last_name>Manuela Zanni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona</name>
      <address>
        <city>Ancona</city>
        <zip>60126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guido Gini</last_name>
      <email>g.gini@ospedaliriuniti.marche.it</email>
    </contact>
    <contact_backup>
      <last_name>Alessandra Barucca</last_name>
      <email>alessandra.barucca@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Guido Gini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ascoli Piceno - Ospedale C.e G. Mazzoni - U.O.C. di Ematologia</name>
      <address>
        <city>Ascoli Piceno</city>
        <zip>15121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Piero Galieni, MD</last_name>
      <email>piero.galieni@sanita.marche.it</email>
    </contact>
    <investigator>
      <last_name>Pietro Galieni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Aviano - Centro Riferimento Oncologico - S.O.C. Oncologia Medica A</name>
      <address>
        <city>Aviano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michele Spina, MD</last_name>
      <email>mspina@cro.it</email>
    </contact>
    <investigator>
      <last_name>Michele Spina, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Barletta - Ospedale &quot;Monsignor Raffaele Dimiccoli&quot; - Ematologia</name>
      <address>
        <city>Barletta</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giuseppe Tarantini, MD</last_name>
      <email>giuseppetarantini0@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Giuseppe Tarantini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bergamo - Cliniche Humanitas Gavazzeni - Oncologia - Cliniche Humanitas Gavazzeni</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Serena Camilla Dalto</last_name>
      <email>serena.dalto@gavazzeni.it</email>
    </contact>
    <investigator>
      <last_name>Serena Camilla Dalto, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Biella - Ospedale Degli Infermi - S.C. Oncologia</name>
      <address>
        <city>Biella</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Annarita Conconi, MD</last_name>
      <email>annarita.conconi@aslbi.piemonte.it</email>
    </contact>
    <investigator>
      <last_name>Annarita Conconi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Campobasso - Universitа Cattolica del Sacro Cuore - Ematologia</name>
      <address>
        <city>Campobasso</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sergio Storti, MD</last_name>
      <email>sergio.storti@unicatt.it</email>
    </contact>
    <investigator>
      <last_name>Sergio Storti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Castelfranco Veneto - Ospedale di Castelfranco Veneto - Ematologia</name>
      <address>
        <city>Castelfranco Veneto</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Roberto Sartori, MD</last_name>
      <email>roberto.sartori@iov.veneto.it</email>
    </contact>
    <investigator>
      <last_name>Roberto Sartori, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Unità Funzionale di Ematologia AOU Careggi</name>
      <address>
        <city>Firenze</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benedetta Puccini, MD</last_name>
      <email>puccinib@aou-careggi.toscana.it</email>
    </contact>
    <investigator>
      <last_name>Benedetta Puccini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Frosinone - Presidio Ospedaliero F. Spaziani - UOC Ematologia</name>
      <address>
        <city>Frosinone</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Gabriella Tomei, MD</last_name>
      <email>gintomei@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Gabriella Tomei, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Matera - Ospedale Madonna delle Grazie - Ematologia</name>
      <address>
        <city>Matera</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Clara Mannarella, MD</last_name>
      <email>clara.mannarella@virgilio.it</email>
    </contact>
    <investigator>
      <last_name>Clara Mannarella, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Meldola - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia</name>
      <address>
        <city>Meldola</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabio Augello, MD</last_name>
      <email>accursio.augello@irst.emr.it</email>
    </contact>
    <investigator>
      <last_name>Fabio Augello, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mestre - Ospedale Dell Angelo - U.O. Ematologia</name>
      <address>
        <city>Mestre</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Renato Bassan, MD</last_name>
      <email>renato.bassan@aulss3.veneto.it</email>
    </contact>
    <investigator>
      <last_name>Renato Bassan, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>SC Ematologia AO Niguarda Cà Granda</name>
      <address>
        <city>Milano</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Emanuele Ravano, MD</last_name>
      <email>emanuele.ravano@ospedaleniguarda.it</email>
    </contact>
    <contact_backup>
      <last_name>Isabella Ghislandi</last_name>
      <email>isabella.ghislandi@ospedaleniguarda.it</email>
    </contact_backup>
    <investigator>
      <last_name>Emanuele Ravano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Monza - ASST MONZA Ospedale S. Gerardo - Ematologia</name>
      <address>
        <city>Monza</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ivana Casaroli, MD</last_name>
      <email>ivanacasaroli@yahoo.it</email>
    </contact>
    <investigator>
      <last_name>Ivana Casaroli, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Napoli - AOU Universitа degli Studi della Campania Luigi Vanvitelli - Oncologia Medica ed Ematologia</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antonello Sica, MD</last_name>
      <email>antonello.sica@fastwebnet.it</email>
    </contact>
    <investigator>
      <last_name>Antonello Sica, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Università del Piemonte Orientale - Novara</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Gianluca Gaidano, MD</last_name>
      <phone>0321/660655</phone>
      <email>gianluca.gaidano@med.uniupo.it</email>
    </contact>
    <contact_backup>
      <last_name>Clara Deambrogi</last_name>
      <email>clara.deambrogi@med.uniupo.it</email>
    </contact_backup>
    <investigator>
      <last_name>Gianluca Gaidano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Padova - I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1</name>
      <address>
        <city>Padova</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dario Marino, MD</last_name>
      <email>dario.marino@iov.veneto.it</email>
    </contact>
    <investigator>
      <last_name>Dario Marino, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Pagani - Presidio ospedaliero &quot;A. TORTORA&quot; - U.O. Onco-ematologia</name>
      <address>
        <city>Pagani</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Catello Califano, MD</last_name>
      <email>c.califano@aslsalerno.it</email>
    </contact>
    <investigator>
      <last_name>Catello Califano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Palermo - A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Caterina Patti, MD</last_name>
      <email>k.patti@villasofia.it</email>
    </contact>
    <investigator>
      <last_name>Caterina Patti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Palermo - AOU Policlinico Giaccone - Ematologia</name>
      <address>
        <city>Palermo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Salvatrice Mancuso, MD</last_name>
      <email>salvatrice.mancuso@unipa.it</email>
    </contact>
    <investigator>
      <last_name>Salvatrice Mancuso, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UO Ematologia Università - Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luca Arcaini, MD</last_name>
      <email>luca.arcaini@unipv.it</email>
    </contact>
    <investigator>
      <last_name>Luca Arcaini, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Pescara - P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi</name>
      <address>
        <city>Pescara</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elsa Pennese, MD</last_name>
      <email>elsapennese@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Stefania Luciani</last_name>
      <email>stefyluciani@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Elsa Pennese, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Potenza - AOR San Carlo</name>
      <address>
        <city>Potenza</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michele Cimminiello, MD</last_name>
      <email>miki-doc@virgilio.it</email>
    </contact>
    <investigator>
      <last_name>Michele Ciminiello, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UO Ematologia Ospedale Santa Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Monica Tani, MD</last_name>
      <email>monica.tani@auslromagna.it</email>
    </contact>
    <investigator>
      <last_name>Monica Tani, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Reggio Emilia - AO Santa Maria Nuova</name>
      <address>
        <city>Reggio Emilia</city>
        <zip>42123</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesco Merli, MD</last_name>
      <phone>0522-296618</phone>
      <email>merli.francesco@asmn.re.it</email>
    </contact>
    <contact_backup>
      <last_name>Caterina Mammi</last_name>
      <email>mammi.caterina@ausl.re.it</email>
    </contact_backup>
    <investigator>
      <last_name>Francesco Merli, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UO Ematologia - Ospedale degli Infermi</name>
      <address>
        <city>Rimini</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Anna Lia Molinari, MD</last_name>
      <email>annalia.molinari@auslromagna.it</email>
    </contact>
    <investigator>
      <last_name>Anna Lia Molinari, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Roma - IRCCS Spallanzani - Servizio di Ematologia in malattie infettive</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michele Bibas, MD</last_name>
      <email>michele.bibas@inmi.it</email>
    </contact>
    <investigator>
      <last_name>Michele Bibas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Roma - Ospedale S. Camillo - Ematologia</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Luigi Rigacci, MD</last_name>
      <email>lrigacci@scamilloforlanini.rm.it</email>
    </contact>
    <investigator>
      <last_name>Luigi Rigacci, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Roma - Policlinico Universitario Campus Bio-Medico - Ematologia - Trapianto cellule staminali - Medicina Trasfusionale e Terapia cellulare</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ombretta Annibali, MD</last_name>
      <email>o.annibali@unicampus.it</email>
    </contact>
    <investigator>
      <last_name>Ombretta Annibali, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Università Cattolica S. Cuore, Ematologia</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Stefan Hohaus, MD</last_name>
      <email>stefan.hohaus@Unicatt.it</email>
    </contact>
    <investigator>
      <last_name>Stefan Hohaus, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Università La Sapienza Ematologia</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alice Di Rocco, MD</last_name>
      <email>dirocco@bce.uniroma1.it</email>
    </contact>
    <investigator>
      <last_name>Alice Di Rocco, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UOC Ematologia - A.O. Sant'Andrea</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Agostino Tafuri, MD</last_name>
      <phone>0633775113</phone>
      <email>agostino.tafuri@ospedalesantandrea.it</email>
    </contact>
    <investigator>
      <last_name>Agostino Tafuri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Salerno - Ematologia e Trapianti A.O. San Giovanni di Dio e Ruggi D Aragona - U.O. Ematologia</name>
      <address>
        <city>Salerno</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carmine Selleri, MD</last_name>
      <email>cselleri@unisa.it</email>
    </contact>
    <investigator>
      <last_name>Carmine Selleri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>San Giovanni Rotondo - Casa Sollievo della Sofferenza - U.O. Ematologia</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicola Cascavilla, MD</last_name>
      <email>n.cascavilla@operapadrepio.it</email>
    </contact>
    <investigator>
      <last_name>Nicola Cascavilla, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sassari - AOU di Sassari - Ematologia</name>
      <address>
        <city>Sassari</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudio Fozza, MD</last_name>
      <email>cfozza@uniss.it</email>
    </contact>
    <investigator>
      <last_name>Claudio Fozza, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UOC Medicina Interna MO DH Oncologico</name>
      <address>
        <city>Sassuolo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sara Bigliardi, MD</last_name>
      <email>s.bigliardi@ausl.mo.it</email>
    </contact>
    <investigator>
      <last_name>Sara Bigliardi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UOC Ematologia, AOU Senese</name>
      <address>
        <city>Siena</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alberto Fabbri, MD</last_name>
      <email>a.fabbri@ao-siena.toscana.it</email>
    </contact>
    <contact_backup>
      <last_name>Cristiana Cafarelli</last_name>
      <email>cristianacafarelli21@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Alberto Fabbri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Univ. Perugia Sede Terni - Oncoematologia</name>
      <address>
        <city>Terni</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Marina Liberati, MD</last_name>
      <email>marina.liberati@unipg.it</email>
    </contact>
    <investigator>
      <last_name>Anna Marina Liberati, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>AOU Citta della Salute e della Scienza di Torino - Ematologia Universitaria</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Federica Cavallo, MD</last_name>
      <phone>+39 0116334264</phone>
      <email>f.cavallo@unito.it</email>
    </contact>
    <contact_backup>
      <last_name>Luca Palumbo</last_name>
    </contact_backup>
    <investigator>
      <last_name>Federica Cavallo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>SC. Ematologia A.O. Città della Salute e della Scienza</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Barbara Botto, MD</last_name>
      <email>bbotto@cittadellasalute.to.it</email>
    </contact>
    <contact_backup>
      <last_name>Giorgio Priolo</last_name>
    </contact_backup>
    <investigator>
      <last_name>Barbara Botto, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Torino - San Giovanni Bosco - ASL Cittа di Torino - SSD di Ematologia e Malattie Trombotiche</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Federica De marco, MD</last_name>
      <email>federica.demarco@aslcittaditorino.it</email>
    </contact>
    <investigator>
      <last_name>Federica De marco, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Trieste - Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) - SC Ematologia</name>
      <address>
        <city>Trieste</city>
        <zip>34121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesco Zaja, MD</last_name>
      <email>francesco.zaja@asuits.sanita.fvg.it</email>
    </contact>
    <contact_backup>
      <last_name>Marta De Piccoli</last_name>
      <email>martadepiccoli1810@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Francesco Zaja, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Udine - Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Clinica Ematologica</name>
      <address>
        <city>Udine</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jacopo Olivieri, MD</last_name>
      <email>jacopo.olivieri@hotmail.it</email>
    </contact>
    <contact_backup>
      <last_name>Cristina D'Odorico</last_name>
      <email>cristina.dodorico@asuiud.sanita.fvg.it</email>
    </contact_backup>
    <investigator>
      <last_name>Jacopo Olivieri, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ULSS 8 Berica - Ospedale S. Bortolo - Ematologia</name>
      <address>
        <city>Vicenza</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Chiara Tisi, MD</last_name>
      <email>mariachiara.tisi@aulss8.veneto.it</email>
    </contact>
    <investigator>
      <last_name>Maria Chiara Tisi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>August 23, 2022</last_update_submitted>
  <last_update_submitted_qc>August 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin D</keyword>
  <keyword>prednisone +/- Vitamin D supplementation</keyword>
  <keyword>randomized, open label, phase III</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, B-Cell</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>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1:1 ratio to Arm A (Standard arm) or Arm B (Experimental arm). All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment (CGA) result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.</ipd_description>
  </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/NCT04442412
org study id: FIL_PREVID
nct id: NCT04442412
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is an open-label, multicenter, randomized phase III trial. The study plans to randomize
      patients with a 1 to 1 ratio to Arm A (Standard arm) or Arm B (Experimental arm).

      All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of
      immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental
      arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD
      during the intere period of immunochemotherapy according to a prefixed schedule. Choice of
      type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment result, but
      treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL
      patients.
After the patient signs the written informed consent the patient will enter the screening
      phase planning baseline assessments and will be randomly allocated with a 1 to 1 ratio to Arm
      A (Standard arm) or Arm B (Experimental arm).

      Patients randomized to Arm A will receive a prephase with oral prednisone (50 mg for 7 days
      [day -6 to day 0]) followed by 6 courses of R-CHOP or R-miniCHOP every 21 days.

      If patients randomized to arm A are already on VitD, they are allowed to continue receiving
      VitD supplementation at a dose that can be considered part of the standard of care and does
      not exceed the maximum standard VitD dose recommended for general adult and elderly
      population , up to 10,000 U/week VitD .

      If clinically indicated at treating physician judgement, patients could receive 1 mg of
      vincristine on the first day of prephase ; in this case vincristine administration in cycle 1
      of immunochemotherapy should be skipped, in patients receiving R-miniCHOP; reduced to 1 mg,
      in patients receiving R-CHOP.

      Patients randomized to Arm B will receive a prephase with oral prednisone and a prephase
      therapy with VitD according to the below reported schedule followed by 6 courses of R-CHOP or
      R-miniCHOP every 21 days.

      Schedule for VitD (Cholecalciferol) supplementation: 25,000 U/day starting on day -6:

      daily loading dose for 7 days if 25 VitD baseline level 20-40 ng/ml daily loading dose for 14
      days if 25 VitD baseline level < 20 ng/ml followed by weekly maintenance supplementation of
      25,000 U for the entire duration of immunochemotherapy (6 courses every 21 days - 18 weeks),
      regardless of the baseline level of 25 VitD.

      If clinically indicated at treating physician judgement, patients could receive 1 mg of
      vincristine on the first day of prephase (DAY -6); in this case vincristine administration in
      cycle 1 of immunochemotherapy should be: skipped, in patients receiving R-miniCHOP; reduced
      to 1 mg, in patients receiving R-CHOP.

      Patients with 25(OH)VitD levels <30 ng/ml on d1 cycle 2 will receive and additional loading
      phase of Cholecalciferol 25,000 U/day for 7 days and then 25,000 U once weekly for the
      duration of immunochemotherapy.

      Patients may continue with VitD supplementation after the end of the immunochemotherapy at a
      (reduced) standard dose of 25,000 U once a month for up to 2 years from end of
      immunochemotherapy.

      Patients experimenting toxicity leading to a delay in treatment administration > 4 weeks will
      discontinue study treatment and will be addressed to a salvage treatment: these patients will
      be followed-up for survival until the end of the study.

      Consolidation radiotherapy:
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1 to 1 ratio to Arm A (Standard arm) or Arm B (Experimental arm). All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-Free Survival
time frame: at the end of treatment - 54 months
description: Progression-Free Survival
measure: Overall Survival
time frame: at the end of treatment - 54 months
description: Overall Survival
measure: Event Free Survival
time frame: at the end of treatment - 54 months
description: Event Free Survival (EFS)
measure: Response rate
time frame: at the end of treatment - 54 months
description: Response rate
measure: Early death rate
time frame: at the end of treatment - 54 months
description: Early death rate
measure: Rate of ECOG changes after prephase
time frame: at the end of treatment - 54 months
description: Rate of ECOG changes after prephase
measure: Rate of patients who maintain 25(OH)VitD levels
time frame: At the beginning of Cycle 2 (each cycle is 21 days)
description: Rate of patients who maintain 25(OH)VitD levels
measure: Rate of 25(OH)VitD correction (VitD supplementation arm)
time frame: At the beginning of Cycle 2 (each cycle is 21 days)
description: Rate of 25(OH)VitD correction (VitD supplementation arm)
measure: time-to-deterioration physical functioning and fatigue
time frame: At the beginning of Cycle 2 (each cycle is 21 days)
description: time-to-deterioration physical functioning and fatigue
arm group label: Arm B (Experimental):
arm group type: Experimental
description: Patients randomized to Arm B will receive a prephase with oral prednisone and a prephase therapy with VitD according to the below reported schedule followed by 6 courses of R-CHOP or R-miniCHOP every 21 days.
Schedule for VitD supplementation: 25,000 U/day starting on day -6:
daily loading dose for 7 days if 25 VitD baseline level 20-40 ng/ml daily loading dose for 14 days if 25 VitD baseline level < 20 ng/ml followed by weekly maintenance supplementation of 25,000 U for the entire duration of immunochemotherapy (6 courses every 21 days - 18 weeks), regardless of the baseline level of 25 VitD.
arm group label: Arm A (Standard arm)
arm group type: Other
description: Patients randomized to Arm A will receive a prephase with oral prednisone followed by 6 courses of R-CHOP or R-miniCHOP every 21 days.
If patients randomized to arm A are already on VitD, they are allowed to continue receiving VitD supplementation at a dose that can be considered part of the standard of care and does not exceed the maximum standard VitD dose recommended for general adult and elderly population , up to 10,000 U/week VitD
intervention type: Drug
intervention name: Vitamin D3 (Cholecalciferol)
description: patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment (CGA) result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.
arm group label: Arm B (Experimental):
intervention type: Drug
intervention name: RCHOP o R-miniCHOP at standard doses
description: Patients on both arms receive pre-treatment with prednisone oral before 6 cycles of 21 days each of immunochemotherapy with RCHOP
o R-miniCHOP at standard doses
arm group label: Arm A (Standard arm)
arm group label: Arm B (Experimental):
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Francesco Merli, Dott.
role: Principal Investigator
affiliation: Reggio Emilia - Azienda Unitа Sanitaria Locale-IRCCS
last name: Lorenza Randi, Dott.ssa
phone: 0000000000
email: lrandi@filinf.it
last name: Francesco Merli, Dott.
phone: 0000000000
email: startup@filinf.it
facility: 
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country: Italy
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Vitamin D
mesh term: Cholecalciferol
sharing ipd: No
ipd description: This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1:1 ratio to Arm A (Standard arm) or Arm B (Experimental arm). All patients of both arms will receive a prephase with oral prednisone before 6 cycles Q21 of immunochemotherapy with R-CHOP or R-miniCHOP at standard doses; patients in the Experimental arm (Arm B) will receive also a prephase therapy with VitD and a supplementation of VitD during the intere period of immunochemotherapy according to a prefixed schedule. Choice of type of immunochemotherapy will not rely on Comprehensive Geriatric Assessment (CGA) result, but treatment at reduced doses with R-miniCHOP is highly recommended option for UNFIT and FRAIL patients.