<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/NCT04446962</url>
  </required_header>
  <id_info>
    <org_study_id>IC 2019-02</org_study_id>
    <secondary_id>2019-003632-23</secondary_id>
    <nct_id>NCT04446962</nct_id>
  </id_info>
  <brief_title>LOC-R01 Study of Lenalidomide and Ibrutinib in Association With Rituximab-Methotrexate Procarbazine Vincristin (R-MPV)</brief_title>
  <acronym>LOC-R01</acronym>
  <official_title>LOC-R01: Randomized Phase IB/II Study of Escalating Doses of Lenalidomide and Ibrutinib in Association With R-MPV as a Targeted Induction Treatment for Patients Aged 18 to 60 (up to 65 for Phase II) With a Newly Diagnosed Primary Central Nervous System Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Curie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut Curie</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 to improve the first-line induction chemotherapy, by combining either&#xD;
      Ibrutinib, or Lenalidomide, to a conventional immuno- chemotherapy of R-MPV type&#xD;
      (Rituximab-Methotrexate-Procarbazine-Vincristine). This is a randomized Phase II trial,&#xD;
      preceded by a dose escalation phase Ib. The objective of the phase Ib is to rule out any&#xD;
      limiting toxicity of the new treatment associations, and to determine the recommended dose of&#xD;
      Lenalidomide and Ibrutinib to be used in the phase II. In the phase II study, patients will&#xD;
      receive 4 cycles of R-MPV + Lenalidomide or 4 cycles of R-MPV + Ibrutinib. The therapeutic&#xD;
      response will be evaluated after the 2nd and the 4th cycle. Patients in good therapeutic&#xD;
      response will proceed to the consolidation phase with Autologous Stem Cell Transplantation&#xD;
      (ASCT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this proposal is to test the feasibility and efficacy of two targeted&#xD;
      induction chemotherapies obtained by adding either Lenalidomide or Ibrutinib to a standard&#xD;
      Rituximab-High Dose (HD) Methotrexate (MTX) based induction chemotherapy regimen. The R-MPV&#xD;
      regimen is chosen as the backbone chemotherapy because of its wide use with robust&#xD;
      reproducible results and a good and manageable toxicity profile&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 30, 2020</start_date>
  <completion_date type="Anticipated">January 15, 2031</completion_date>
  <primary_completion_date type="Anticipated">January 15, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm.</measure>
    <time_frame>1 month</time_frame>
    <description>Occurrence of a Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm. The phase Ib is a 3+3 dose escalation design</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Response (CR) rate including unconfirmed Complete Response (uCR) at the end of the 4 cycles of induction therapy</measure>
    <time_frame>4 months</time_frame>
    <description>The primary endpoint for the phase II part of the study is the Complete Response (CR) rate including unconfirmed CR (CR+uCR) at the end of the 4 cycles of induction therapy. Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rates (CR + uCR) after 2 cycles of induction treatment</measure>
    <time_frame>2 months</time_frame>
    <description>Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response (CR + uCR + Partial Response(PR)), stable disease (SD), and primary refractory patients (PD) after 2 cycles of induction treatment</measure>
    <time_frame>2 months</time_frame>
    <description>Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response (CR + uCR + Partial Response(PR)), stable disease (SD), and primary refractory patients (PD) after 4 cycles of induction treatment</measure>
    <time_frame>4 months</time_frame>
    <description>Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>142 months</time_frame>
    <description>Overall Survival (OS) will be calculated from the date of randomization to the date of death, whatever the cause. Patients alive at the date of last contact will be censored at this date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>142 months</time_frame>
    <description>Progression-Free Survival (PFS) will be calculated from the date of randomization to the date of progression or death (if the patient does not progress). Patients alive without progression at the date of last contact will be censored at this date</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The severity of the toxicity of treatment induction or ASCT</measure>
    <time_frame>7 months</time_frame>
    <description>Toxicity of treatment induction or ASCT will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 5.0) whenever possible and described by system organ class, preferred term</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients who will receive ASCT</measure>
    <time_frame>7 months</time_frame>
    <description>The percentage of patients who will receive ASCT will be presented</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">128</enrollment>
  <condition>Lymphoma, Large B-Cell, Diffuse</condition>
  <condition>Central Nervous System Neoplasms, Primary</condition>
  <arm_group>
    <arm_group_label>Arm A: R-MPV with Lenalidomide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lenalidomide in association with R-MPV as a targeted induction treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: R-MPV with Ibrutinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ibrutinib in association with R-MPV as a targeted induction treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Patients will receive 4 cycles of induction chemotherapy with R-MPV + Lenalidomide using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.</description>
    <arm_group_label>Arm A: R-MPV with Lenalidomide</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Patients will receive 4 cycles of induction chemotherapy with R-MPV + Ibrutinib, using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.</description>
    <arm_group_label>Arm B: R-MPV with Ibrutinib</arm_group_label>
    <other_name>Imbruvica</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).&#xD;
&#xD;
          2. a) Aged between 18 and 60 (&gt;18 and &lt; 60) - phase IB b) Aged between 18 and 65 (≥ 18&#xD;
             and ≤ 65) - phase II.&#xD;
&#xD;
          3. Histological confirmed diagnosis of Primary central nervous system lymphoma of Diffuse&#xD;
             Large B-Cell Lymphomas (DLBCL) type OR patients with a measurable typical cerebral&#xD;
             lesion on MRI with a diagnosis made by cytology and/or by flow cytometry on the&#xD;
             vitreous or on the cerebral spinal fluid.&#xD;
&#xD;
          4. Measurable lesion on MRI with gadolinium enhancement.&#xD;
&#xD;
          5. Adequate hematological, renal and hepatic function (Laboratory Parameters realized&#xD;
             within 14 days before inclusion):&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) &gt;1000/mm3&#xD;
&#xD;
               2. Platelets &gt; 100,000/mm3 independent of transfusion support&#xD;
&#xD;
               3. Alanine aminotransferase and aspartate aminotransferase ≤ 3 x Upper Limit of&#xD;
                  Normal (ULN)&#xD;
&#xD;
               4. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or&#xD;
                  of non-hepatic origin&#xD;
&#xD;
               5. Estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73m2.&#xD;
&#xD;
          6. Able to swallow capsules.&#xD;
&#xD;
          7. Karnofsky performance status: 40-100% for the phase IB and no restriction on the KPS&#xD;
             for the phase II.&#xD;
&#xD;
          8. Able to understand teratogenic risks of the Lenalidomide and Ibrutinib. Patient must&#xD;
             be able to understand and fulfill the Lenalidomide Pregnancy Prevention Plan&#xD;
             requirements. This plan may be accepted by the person of confidence in case of&#xD;
             impaired cognitive status of the patient.&#xD;
&#xD;
          9. Women of childbearing potential (WCBP)* and men who are sexually active must be&#xD;
             practicing a highly effective method** of birth control. Women should avoid a&#xD;
             pregnancy while taking treatment by Lenalidomide or Ibrutinib and for up to 1 month&#xD;
             after ending treatment. Men must agree to not to father a child or donate sperm during&#xD;
             treatment by Lenalidomide or Ibrutinib and up to 3 months after the last dose of study&#xD;
             drug.&#xD;
&#xD;
         10. Women of childbearing potential (WCBP)* must have a negative serum (beta-human&#xD;
             chorionic gonadotropin [B-hCG]) or urine pregnancy test at inclusion.&#xD;
&#xD;
         11. Signed informed consent, which could be signed by a person on confidence in case the&#xD;
             neurologic status of the patient does not allow him to understand and/or to sign.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histology other than DLBCL.&#xD;
&#xD;
          2. Positive HIV serology.&#xD;
&#xD;
          3. Active viral infection with Hepatitis B or C virus.&#xD;
&#xD;
          4. Preexisting immunodeficiency and/or organ transplant recipient.&#xD;
&#xD;
          5. Isolated Central Nervous System (CNS) relapse of systemic Non-Hodgkin's Lymphoma.&#xD;
&#xD;
          6. Prior treatment for PCNSL (except corticosteroids).&#xD;
&#xD;
          7. Isolated primary vitreo-retinal lymphoma.&#xD;
&#xD;
          8. Major surgery, within 4 weeks prior to the first dose of study drug. Stereotactic&#xD;
             biopsy and vitrectomy are not considered major surgery.&#xD;
&#xD;
          9. History of stroke or intracranial hemorrhage (except minor post biopsy hemorrhage)&#xD;
             within 6 months prior to inclusion.&#xD;
&#xD;
         10. Requires anticoagulation with warfarin or equivalent vitamin K antagonists.&#xD;
&#xD;
         11. Requires treatment with strong CYP3A4 inhibitors.&#xD;
&#xD;
         12. Pregnancy or lactation.&#xD;
&#xD;
         13. Clinically significant cardiovascular disease.&#xD;
&#xD;
         14. Any other active malignancy, except basocellular carcinoma and non-invasive cervix&#xD;
             cancer.&#xD;
&#xD;
         15. Inclusion in another experimental anti-cancer drug therapy.&#xD;
&#xD;
         16. No social security affiliation.&#xD;
&#xD;
         17. Persons under legal protection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven LE GOUILL, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institut Curie</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carole SOUSSAIN, MD</last_name>
    <phone>+33 1 47 11 15 15</phone>
    <email>carole.soussain@curie.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Christine FOULON</last_name>
    <phone>+33 1 47 11 17 33</phone>
    <email>drci.promotion@curie.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU Amiens</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caroline DELETTE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Caroline DELETTE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Angers</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jérôme PAILLASSA, MD</last_name>
    </contact>
    <contact_backup>
      <email>jerome.paillassa@chu-angers.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Jérôme PAILLASSA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH côte Basque</name>
      <address>
        <city>Bayonne</city>
        <zip>64100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sophie BERNARD, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sophie BERNARD, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Besançon</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adrien CHAUCHET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Adrien CHAUCHET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna SCHMITT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Anna SCHMITT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Caen</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gandhi DAMAJ, MD</last_name>
    </contact>
    <investigator>
      <last_name>Gandhi DAMAJ, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cécile MOLUCON-CHABROT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Cécile MOLUCON-CHABROT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH Colmar</name>
      <address>
        <city>Colmar</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guido AHLE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Guido AHLE Guido AHLE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Créteil</name>
      <address>
        <city>Créteil</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Louise ROULIN, MD</last_name>
    </contact>
    <investigator>
      <last_name>Louise ROULIN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Dijon</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rémy Rémy GRESSIN, MD</last_name>
    </contact>
    <investigator>
      <last_name>Rémy GRESSIN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU Lille</name>
      <address>
        <city>Lille</city>
        <zip>69000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Franck MORSCHHAUSER, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Franck MORSCHHAUSER, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julie ABRAHAM, MD</last_name>
    </contact>
    <investigator>
      <last_name>ABRAHAM Julie, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hervé GHESQUIERES, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hervé GHESQUIERES, Phd</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU La Timone Marseille</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier CHINOT, MD</last_name>
    </contact>
    <investigator>
      <last_name>Olivier CHINOT, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Nancy</name>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luc TAILLANDIER, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Luc TAILLANDIER, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas GASTINNE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Thomas GASTINNE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Lacassagne</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frédéric PEYRADE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Frédéric PEYRADE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Nîmes - Carémeau</name>
      <address>
        <city>Nîmes</city>
        <zip>30029</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Agathe WAULTIER-RASCALOU, MD</last_name>
    </contact>
    <investigator>
      <last_name>Agathe WAULTIER-RASCALOU, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carole Soussain, MD</last_name>
    </contact>
    <investigator>
      <last_name>Carole Soussain, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75006</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lise WILLEMS, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lise WILLEMS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caroline HOUILLIER, MD</last_name>
    </contact>
    <investigator>
      <last_name>Caroline HOUILLIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Poitiers</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vincent DELWAIL, MD</last_name>
    </contact>
    <investigator>
      <last_name>Vincent DELWAIL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thierry LAMY De La CHAPELLE, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Thierry Thierry LAMY De La CHAPELLE, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Henri Becquerel</name>
      <address>
        <city>Rouen</city>
        <zip>76000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabrice JARDIN, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Fabrice JARDIN, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>IUCT -Oncopole</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lucie Obéric, MD</last_name>
    </contact>
    <investigator>
      <last_name>Lucie Obéric, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Tours</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emmanuel GYAN, MD</last_name>
    </contact>
    <investigator>
      <last_name>Emmanuel GYAN, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>November 30, 2022</last_update_submitted>
  <last_update_submitted_qc>November 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lymphoma</keyword>
  <keyword>Nervous System</keyword>
  <keyword>Primary</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Central Nervous System Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04446962
org study id: IC 2019-02
secondary id: 2019-003632-23
nct id: NCT04446962
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is to improve the first-line induction chemotherapy, by combining either
      Ibrutinib, or Lenalidomide, to a conventional immuno- chemotherapy of R-MPV type
      (Rituximab-Methotrexate-Procarbazine-Vincristine). This is a randomized Phase II trial,
      preceded by a dose escalation phase Ib. The objective of the phase Ib is to rule out any
      limiting toxicity of the new treatment associations, and to determine the recommended dose of
      Lenalidomide and Ibrutinib to be used in the phase II. In the phase II study, patients will
      receive 4 cycles of R-MPV + Lenalidomide or 4 cycles of R-MPV + Ibrutinib. The therapeutic
      response will be evaluated after the 2nd and the 4th cycle. Patients in good therapeutic
      response will proceed to the consolidation phase with Autologous Stem Cell Transplantation
      (ASCT).
The objective of this proposal is to test the feasibility and efficacy of two targeted
      induction chemotherapies obtained by adding either Lenalidomide or Ibrutinib to a standard
      Rituximab-High Dose (HD) Methotrexate (MTX) based induction chemotherapy regimen. The R-MPV
      regimen is chosen as the backbone chemotherapy because of its wide use with robust
      reproducible results and a good and manageable toxicity profile
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm.
time frame: 1 month
description: Occurrence of a Dose Limiting Toxicity (DLT) during the first cycle of treatment for each treatment arm. The phase Ib is a 3+3 dose escalation design
measure: Complete Response (CR) rate including unconfirmed Complete Response (uCR) at the end of the 4 cycles of induction therapy
time frame: 4 months
description: The primary endpoint for the phase II part of the study is the Complete Response (CR) rate including unconfirmed CR (CR+uCR) at the end of the 4 cycles of induction therapy. Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)
measure: Response rates (CR + uCR) after 2 cycles of induction treatment
time frame: 2 months
description: Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)
measure: Overall response (CR + uCR + Partial Response(PR)), stable disease (SD), and primary refractory patients (PD) after 2 cycles of induction treatment
time frame: 2 months
description: Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)
measure: Overall response (CR + uCR + Partial Response(PR)), stable disease (SD), and primary refractory patients (PD) after 4 cycles of induction treatment
time frame: 4 months
description: Assessment of response will be based on the International Primary Central Nervous System Lymphoma Collaborative Group (IPCG)
measure: Overall Survival (OS)
time frame: 142 months
description: Overall Survival (OS) will be calculated from the date of randomization to the date of death, whatever the cause. Patients alive at the date of last contact will be censored at this date.
measure: Progression-Free Survival (PFS)
time frame: 142 months
description: Progression-Free Survival (PFS) will be calculated from the date of randomization to the date of progression or death (if the patient does not progress). Patients alive without progression at the date of last contact will be censored at this date
measure: The severity of the toxicity of treatment induction or ASCT
time frame: 7 months
description: Toxicity of treatment induction or ASCT will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 5.0) whenever possible and described by system organ class, preferred term
measure: Patients who will receive ASCT
time frame: 7 months
description: The percentage of patients who will receive ASCT will be presented
arm group label: Arm A: R-MPV with Lenalidomide
arm group type: Active Comparator
description: Lenalidomide in association with R-MPV as a targeted induction treatment
arm group label: Arm B: R-MPV with Ibrutinib
arm group type: Active Comparator
description: Ibrutinib in association with R-MPV as a targeted induction treatment
intervention type: Drug
intervention name: Lenalidomide
description: Patients will receive 4 cycles of induction chemotherapy with R-MPV + Lenalidomide using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.
arm group label: Arm A: R-MPV with Lenalidomide
other name: Revlimid
intervention type: Drug
intervention name: Ibrutinib
description: Patients will receive 4 cycles of induction chemotherapy with R-MPV + Ibrutinib, using the Maximum Tolerated Dose (MTD) of Lenalidomide and Ibrutinib as determined in the phase-Ib part of the study.
arm group label: Arm B: R-MPV with Ibrutinib
other name: Imbruvica
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Steven LE GOUILL, PhD
role: Study Director
affiliation: Institut Curie
last name: Carole SOUSSAIN, MD
phone: +33 1 47 11 15 15
email: carole.soussain@curie.fr
last name: Christine FOULON
phone: +33 1 47 11 17 33
email: drci.promotion@curie.fr
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Terminated
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Nervous System Neoplasms
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Central Nervous System Neoplasms
mesh term: Lenalidomide