xml: <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/NCT05998642</url>
    </required_header>
    <id_info>
      <org_study_id>I244</org_study_id>
      <nct_id>NCT05998642</nct_id>
    </id_info>
    <brief_title>Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma</brief_title>
    <official_title>A Phase 2 Study of Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary Central Nervous System Lymphoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Canadian Cancer Trials Group</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Janssen Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Canadian Cancer Trials 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 being done to answer the following question: Can the addition of a new drug to&#xD;
        the usual treatment lower the chance of primary central nervous system lymphoma growing or&#xD;
        spreading?&#xD;
  &#xD;
        We are doing this study because we want to find out if this approach is better or worse than&#xD;
        the usual approach for this type of cancer. The usual approach is defined as care most people&#xD;
        get for Primary Central Nervous System Lymphoma (PCNSL).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        If a patient decides to take part in this study, they will get 3 months of treatment with&#xD;
        methotrexate and ibrutinib as well as rituximab (if rituximab is given for PCNSL in the&#xD;
        applicable province). This will be followed by treatment with ibrutinib alone for up to 2&#xD;
        years of total treatment time.&#xD;
  &#xD;
        After finishing study treatment, and even if patients stop treatment early, the study doctor&#xD;
        will continue to follow the patient's condition for the rest of their life or until all study&#xD;
        results are known (in approximately 6 years), watch for side effects and keep track of the&#xD;
        patient's health. If there are any side effects that may be related to ibrutinib, the patient&#xD;
        will be asked to come back to the clinic every 3 months until side effects improve. If there&#xD;
        are no side effects from ibrutinib the patient will be asked to come back to clinic every 6&#xD;
        months until cancer worsens, and then every 6 months may be contacted by phone.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 30, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2028</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2028</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>One year progression-free survival (PFS)</measure>
      <time_frame>5 years</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Response Rate (ORR = CR+CRu+PR) and complete response (CR) rate</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>1-year event-free survival (EFS)</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>2-year progression-free survival</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number and severity of adverse events</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To determine the impact on cognitive functioning of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-Cog</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To determine the impact on health-related quality of life of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-BR</measure>
      <time_frame>5 years</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Non-hodgkin Lymphoma</condition>
    <arm_group>
      <arm_group_label>Methotrexate, Ibrutinib +/- Rituximab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Cycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Methotrexate</intervention_name>
      <description>3.5mg/m2 IV</description>
      <arm_group_label>Methotrexate, Ibrutinib +/- Rituximab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Rituximab (where available)</intervention_name>
      <description>375mg/m2 / 1400mg IV or SC</description>
      <arm_group_label>Methotrexate, Ibrutinib +/- Rituximab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ibrutinib</intervention_name>
      <description>Dose and schedule assigned at enrollment</description>
      <arm_group_label>Methotrexate, Ibrutinib +/- Rituximab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients must have histological or cytological evidence of primary central nervous&#xD;
               system (CNS) lymphoma (PCNSL); patients with vitreo-retinal lymphoma (NHL) or&#xD;
               cerebrospinal fluid (CSF) positive disease are eligible providing there is CNS&#xD;
               involvement on MRI compatible with PCNSL&#xD;
  &#xD;
            -  Patients must be 18 years of age or older&#xD;
  &#xD;
            -  Patients must be ineligible (≥65 years old or comorbidities) for high-dose&#xD;
               chemotherapy and autologous stem cell transplantation. Patients must be considered&#xD;
               fit, as determined by the treating physician, to receive high dose methotrexate,&#xD;
               ibrutinib and rituximab as per protocol&#xD;
  &#xD;
            -  Patients must have consented to the release of a tumour block from their brain tumour,&#xD;
               if available (see Section 12.0). The centre/pathologist must have agreed to the&#xD;
               submission of the specimen(s).&#xD;
  &#xD;
            -  No prior systemic therapy other than corticosteroids for PCNSL is permitted. Use of&#xD;
               corticosteroids to control symptoms of PCNSL is allowed, but the patient must be on a&#xD;
               maximum dose of dexamethasone 8mg/day (or equivalent) or less at the time of&#xD;
               enrolment. Patients must wean off the steroids within 7 days of starting the study&#xD;
               protocol treatment&#xD;
  &#xD;
            -  Previous major surgery is permitted provided that surgery occurred at least 28 days&#xD;
               prior to patient enrollment and that wound healing has occurred. The 28 day cut-off&#xD;
               does not apply to surgery for PCNSL; treatment may begin following brain biopsy when&#xD;
               deemed safe by the treating investigator&#xD;
  &#xD;
            -  No prior radiation therapy for PCNSL is allowed&#xD;
  &#xD;
            -  ECOG performance status 0-2, and ECOG 3 permitted if secondary to primary CNS lymphoma&#xD;
               and expected to reverse with treatment&#xD;
  &#xD;
            -  Patients must be able to swallow oral medications and have no known gastrointestinal&#xD;
               disorders that may interfere with absorption (such as malabsorption).&#xD;
  &#xD;
            -  Patients must have adequate organ and marrow function measured within 7 days prior to&#xD;
               enrollment including: Absolute neutrophils &gt; 1.0 x 10^9/L; Platelets ≥ 75 x 10^9/L;&#xD;
               Bilirubin ≤ 1.5 x UNL; ALT ≤ 2.5 x UNL; Creatinine clearance ≥ 50 mL/min&#xD;
  &#xD;
            -  Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life&#xD;
               questionnaire in either English or French&#xD;
  &#xD;
            -  Patients must be accessible for treatment and follow up. Patients enrolled on this&#xD;
               trial must be treated and followed at the participating centre&#xD;
  &#xD;
            -  In accordance with CCTG policy, protocol treatment is to begin within 2 working days&#xD;
               of patient enrollment&#xD;
  &#xD;
            -  Women/men of childbearing potential must have agreed to use a highly effective&#xD;
               contraceptive method.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients with secondary central nervous system non-Hodgkin lymphoma (NHL).&#xD;
  &#xD;
            -  Patients with significant third space accumulation (pleural effusions, ascites) which&#xD;
               cannot be adequately drained in advance of methotrexate administration&#xD;
  &#xD;
            -  Patients with a prior or concurrent malignancy whose natural history or treatment does&#xD;
               not have the potential to interfere with the safety or efficacy assessment of the&#xD;
               investigational regimen are eligible for this trial. However, patients on active&#xD;
               anticancer therapy for other advanced or metastatic malignancies are not eligible.&#xD;
  &#xD;
            -  Patients with a known hypersensitivity to the study drugs or their components&#xD;
  &#xD;
            -  Patients with active or uncontrolled infections or with serious illnesses or medical&#xD;
               conditions which would not permit the patient to be managed according to protocol&#xD;
  &#xD;
            -  Patients may not receive concurrent treatment with other anti-cancer therapy or&#xD;
               investigational agents while on protocol therapy&#xD;
  &#xD;
            -  Patients with prior allogenic bone marrow transplant or double umbilical cord blood&#xD;
               transplantation.&#xD;
  &#xD;
            -  Pregnant or breastfeeding women&#xD;
  &#xD;
            -  Patients requiring:&#xD;
  &#xD;
                 1. Anticoagulation with warfarin or equivalent vitamin K antagonists&#xD;
  &#xD;
                 2. Continued requirement for therapy with a strong CYP3A inhibitor or inducer (see&#xD;
                    trial webpage for list)&#xD;
  &#xD;
                 3. Corticosteroid treatment with &gt; 8mg of dexamethasone (or equivalent) at the time&#xD;
                    of enrollment&#xD;
  &#xD;
                 4. Supplements containing fish oil or vitamin E, and grapefruit juice should be&#xD;
                    avoided&#xD;
  &#xD;
            -  Live attenuated vaccination administered within 30 days prior to enrollment&#xD;
  &#xD;
            -  Patients with clinically significant cardiac disease, including:&#xD;
  &#xD;
                 -  angina pectoris, symptomatic pericarditis, coronary artery bypass grafting,&#xD;
                    coronary angioplasty, or stenting, or myocardial infarction in the previous 12&#xD;
                    months;&#xD;
  &#xD;
                 -  history of documented congestive heart failure (New York Heart Association&#xD;
                    functional classification III-IV) or cardiomyopathy;&#xD;
  &#xD;
                 -  uncontrolled hypertension (per Canadian guidelines);&#xD;
  &#xD;
                 -  atrial or ventricular arrhythmias; patients with controlled atrial fibrillation&#xD;
                    are eligible&#xD;
  &#xD;
            -  Patients with distant clinically significant cardiac history should have a LVEF ≥ 50%&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jean-Francois Larouche</last_name>
      <role>Study Chair</role>
      <affiliation>CHU de Quebec-Hopital l'Enfant-Jesus (HEJ), Quebec City, QC Canada</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Anca Prica</last_name>
      <role>Study Chair</role>
      <affiliation>University Health Network-Princess Margaret Hospital, Toronto, ON Canada</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Annette Hay</last_name>
      <phone>613-533-6430</phone>
      <email>ahay@ctg.queensu.ca</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Central Nervous System</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rituximab</mesh_term>
      <mesh_term>Methotrexate</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05998642
  org study id: I244
  nct id: NCT05998642
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This study is being done to answer the following question: Can the addition of a new drug to
        the usual treatment lower the chance of primary central nervous system lymphoma growing or
        spreading?
  
        We are doing this study because we want to find out if this approach is better or worse than
        the usual approach for this type of cancer. The usual approach is defined as care most people
        get for Primary Central Nervous System Lymphoma (PCNSL).
  If a patient decides to take part in this study, they will get 3 months of treatment with
        methotrexate and ibrutinib as well as rituximab (if rituximab is given for PCNSL in the
        applicable province). This will be followed by treatment with ibrutinib alone for up to 2
        years of total treatment time.
  
        After finishing study treatment, and even if patients stop treatment early, the study doctor
        will continue to follow the patient's condition for the rest of their life or until all study
        results are known (in approximately 6 years), watch for side effects and keep track of the
        patient's health. If there are any side effects that may be related to ibrutinib, the patient
        will be asked to come back to the clinic every 3 months until side effects improve. If there
        are no side effects from ibrutinib the patient will be asked to come back to clinic every 6
        months until cancer worsens, and then every 6 months may be contacted by phone.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: One year progression-free survival (PFS)
  time frame: 5 years
  measure: Overall Response Rate (ORR = CR+CRu+PR) and complete response (CR) rate
  time frame: 5 years
  measure: 1-year event-free survival (EFS)
  time frame: 5 years
  measure: 2-year progression-free survival
  time frame: 5 years
  measure: Overall survival (OS)
  time frame: 5 years
  measure: Number and severity of adverse events
  time frame: 5 years
  measure: To determine the impact on cognitive functioning of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-Cog
  time frame: 5 years
  measure: To determine the impact on health-related quality of life of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-BR
  time frame: 5 years
  arm group label: Methotrexate, Ibrutinib +/- Rituximab
  arm group type: Experimental
  description: Cycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally
  intervention type: Drug
  intervention name: Methotrexate
  description: 3.5mg/m2 IV
  arm group label: Methotrexate, Ibrutinib +/- Rituximab
  intervention type: Drug
  intervention name: Rituximab (where available)
  description: 375mg/m2 / 1400mg IV or SC
  arm group label: Methotrexate, Ibrutinib +/- Rituximab
  intervention type: Drug
  intervention name: Ibrutinib
  description: Dose and schedule assigned at enrollment
  arm group label: Methotrexate, Ibrutinib +/- Rituximab
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jean-Francois Larouche
  role: Study Chair
  affiliation: CHU de Quebec-Hopital l'Enfant-Jesus (HEJ), Quebec City, QC Canada
  last name: Anca Prica
  role: Study Chair
  affiliation: University Health Network-Princess Margaret Hospital, Toronto, ON Canada
  last name: Annette Hay
  phone: 613-533-6430
  email: ahay@ctg.queensu.ca
  responsible party type: Sponsor
  mesh term: Lymphoma
  mesh term: Rituximab
  mesh term: Methotrexate
  sharing ipd: No