<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/NCT02242097</url>
  </required_header>
  <id_info>
    <org_study_id>NU 14H06</org_study_id>
    <secondary_id>NCI-2014-01777</secondary_id>
    <secondary_id>PCI-32765MCL2003</secondary_id>
    <secondary_id>STU00098385</secondary_id>
    <secondary_id>NU 14H06</secondary_id>
    <secondary_id>P30CA060553</secondary_id>
    <nct_id>NCT02242097</nct_id>
  </id_info>
  <brief_title>Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma</brief_title>
  <official_title>A Phase II Clinical Trial Evaluating Ibrutinib Maintenance Following Intensive Induction for Patients With Previously Untreated Mantle Cell Lymphoma (MCL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen Scientific Affairs, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being done to see whether or not a drug called ibrutinib can be given to&#xD;
      patients with mantle cell lymphoma (MCL) as maintenance therapy after induction chemotherapy.&#xD;
      This drug blocks an enzyme that affects how the lymphocytes grow and survive. The&#xD;
      investigators hope to learn how safe and effective ibrutinib is for treating patients with&#xD;
      MCL after responding to induction chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the progression-free survival (PFS) rate after 2 years.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Assess toxicity. II. Determine rates of conversion from partial response (PR) to complete&#xD;
      response (CR).&#xD;
&#xD;
      III. Determine median overall survival (OS) after 4 years.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. Compare minimal residual disease (MRD) results overtime by polymerase chain reaction (PCR)&#xD;
      and correlate these with PFS and OS.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28&#xD;
      days for up to 4 years in the absence of disease progression, unacceptable toxicity or&#xD;
      patient preference.&#xD;
&#xD;
      After completion of study treatment, patients who completed 4 years of treatment are followed&#xD;
      up at 30 days. Patients who did not complete 4 years of treatment are followed up for up to 4&#xD;
      years post-first dose of treatment (every 3 months for 2 years and then every 6 months for 4&#xD;
      years).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>January 2015</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2021</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>Determine the progression-free survival (PFS) rate after 2 years</measure>
    <time_frame>Assessed at 2 years</time_frame>
    <description>PFS will be measured from start of treatment to time of progression. Evidence of clinical progression will be documented by imaging (CT scan) for patients who have measurable disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events, defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0</measure>
    <time_frame>Up to 30 days after completion of study treatment, maximum 4 years post-first dose</time_frame>
    <description>To assess toxicity, all adverse events will be summarized as to type, severity, frequency, timing and attribution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of conversion from Partial Response (PR) to Complete Response (CR)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Progression will be evaluated using Cheson 2007 criteria, only patients who had a PR at the time of registration and who complete ≥ 1 complete cycle of ibrutinib maintenance therapy will be evaluable for this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine median Overall Survival (OS) after 4 years</measure>
    <time_frame>Up to 4 years post-first dose</time_frame>
    <description>Patients will be evaluated monthly for the first 6 months on treatment, then every 3 months thereafter. Patients who go off treatment will continue to be followed for up to 4 years post-first dose. Follow-up will occur every 3 months (up to 2 years after the first dose of treatment) and then every 6 months thereafter (up to 4 years post-first dose). Median OS after 4 years will be calculated.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Compare Minimum Residual Disease (MRD) results overtime by Polymerase Chain Reaction (PCR) and correlate these with PFS and OS</measure>
    <time_frame>Four time-points: baseline (pre-treatment), after 1 month and 6 months of treatment, and approximately 18-24 months post-first dose of treatment</time_frame>
    <description>Archived tissue from a previous biopsy from all patients will be obtained for baseline clone identification; in addition, peripheral whole blood samples will be collected at four time points. MRD analysis will be conducted using PCR methods and results will be compared over time and correlated with PFS and OS.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Contiguous Stage II Mantle Cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Mantle Cell Lymphoma</condition>
  <condition>Stage I Mantle Cell Lymphoma</condition>
  <condition>Stage III Mantle Cell Lymphoma</condition>
  <condition>Stage IV Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (ibrutinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ibrutinib orally PO QD on days 1-28. Courses repeat every 28 days for up to 4 years in the absence of disease progression, unacceptable toxicity, or patient preference.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ibrutinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ibrutinib)</arm_group_label>
    <other_name>Bruton's tyrosine kinase inhibitor PCI-32765</other_name>
    <other_name>BTK inhibitor PCI-32765</other_name>
    <other_name>CRA-032765</other_name>
    <other_name>Imbruvica</other_name>
    <other_name>PCI-32765</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ibrutinib)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically confirmed mantle cell lymphoma (MCL)&#xD;
&#xD;
               -  Please note: Measurable disease is not required, but will be followed if it&#xD;
                  exists&#xD;
&#xD;
          -  Patients must have received 4 or more cycles of one of the following prior systemic&#xD;
             induction chemotherapy regimens:&#xD;
&#xD;
               -  Rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin),&#xD;
                  vincristine sulfate (Oncovin), prednisone (R-CHOP) (with or without alternating&#xD;
                  rituximab, dexamethasone, cytarabine [ara-c], cisplatin [platinum] [R-DHAP]) with&#xD;
                  or without autologous (auto) stem cell transplant (SCT)&#xD;
&#xD;
               -  Hyper-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride&#xD;
                  (adriamycin), dexamethasone (CVAD) with or without auto SCT&#xD;
&#xD;
               -  Bendamustine + rituximab with or without auto SCT&#xD;
&#xD;
                    -  Please note:&#xD;
&#xD;
                         -  Patients who received combinations of the above regimens are not&#xD;
                            eligible for enrollment&#xD;
&#xD;
                         -  At the time of registration, patients must be at least 14 days out from&#xD;
                            last dose of cytotoxic chemotherapy, but no more than 90 days; if a&#xD;
                            patient underwent auto SCT, he/she must demonstrate engraftment (per&#xD;
                            treating investigator's discretion) and must meet all other&#xD;
                            hematological requirements as outlined below&#xD;
&#xD;
          -  Patients must have achieved a response to induction chemotherapy (either CR or PR by&#xD;
             Cheson 2007 criteria) and be without known progression&#xD;
&#xD;
          -  Patients may have received prior radiotherapy&#xD;
&#xD;
          -  Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status&#xD;
             =&lt; 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3, independent of growth factor support&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mm^3, or &gt;= 50,000 in cases of ongoing bone marrow involvement&#xD;
             (in either case, these must be independent of transfusion support)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT])&#xD;
             =&lt; 3 x ULN&#xD;
&#xD;
          -  Creatinine clearance &gt;= 25 ml/min&#xD;
&#xD;
          -  Please note: Patients who do not meet the above criteria because of Gilbert's Syndrome&#xD;
             are still eligible&#xD;
&#xD;
          -  Women of child-bearing potential (WOCBP) and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
             entry and for the duration of study participation (see timelines below for women and&#xD;
             men); in addition, men must agree not to donate sperm during and after study&#xD;
             participation; should a woman become pregnant or suspect she is pregnant while&#xD;
             participating in this study, she should inform her treating physician immediately&#xD;
&#xD;
               -  NOTE: For female patients, these restrictions apply for 1 month after the last&#xD;
                  dose of study drug; for male patients, these restrictions apply for 3 months&#xD;
                  after the last dose of study drug&#xD;
&#xD;
               -  NOTE: A female of child-bearing potential is any woman (regardless of sexual&#xD;
                  orientation, having undergone a tubal ligation, or remaining celibate by choice)&#xD;
                  who meets the following criteria:&#xD;
&#xD;
                    -  Has not undergone a hysterectomy or bilateral oophorectomy; or&#xD;
&#xD;
                    -  Has not been naturally postmenopausal for at least 12 consecutive months&#xD;
                       (i.e., has had menses at any time in the preceding 12 consecutive months)&#xD;
&#xD;
          -  Female patients must have a negative pregnancy test (blood or urine) within 28 days&#xD;
             prior to registration&#xD;
&#xD;
          -  Patients must be willing and able to avoid consuming food and beverages containing&#xD;
             grapefruit or Seville oranges while on ibrutinib study therapy&#xD;
&#xD;
          -  Patients must have the ability to understand and the willingness to sign a written&#xD;
             informed consent prior to registration on study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received &gt;= 7 days of prior ibrutinib or any prior treatment with&#xD;
             another Bruton tyrosine kinase (BTK) inhibitor are not eligible&#xD;
&#xD;
          -  Patients receiving ongoing treatment with any other investigational agents are not&#xD;
             eligible&#xD;
&#xD;
          -  Patients receiving live/attenuated vaccinations within 4 weeks prior to registration&#xD;
             are not eligible&#xD;
&#xD;
          -  Patients with a known central nervous system (CNS) involvement of lymphoma are not&#xD;
             eligible (CNS staging not required)&#xD;
&#xD;
          -  Patients who have undergone major surgery within 4 weeks prior to registration are not&#xD;
             eligible&#xD;
&#xD;
          -  Patients diagnosed or treated for malignancy other than MCL are not eligible unless&#xD;
             they meet one of the following exceptions:&#xD;
&#xD;
               -  Malignancy treated with curative intent and with no known active disease present&#xD;
                  for &gt;= 3 years before registration and felt to be at low risk for recurrence by&#xD;
                  the treating physician&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               -  Adequately treated cervical carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  Patients with a history of stroke or intracranial hemorrhage within 6 months prior to&#xD;
             registration are not eligible&#xD;
&#xD;
          -  Patients who require anticoagulation with warfarin or equivalent vitamin K antagonists&#xD;
             are not eligible&#xD;
&#xD;
          -  Patients who require chronic treatment with strong cytochrome P450, family 3,&#xD;
             subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors are not eligible&#xD;
&#xD;
               -  NOTE: Patients who are currently on treatment with strong CYP3A4/5 inhibitors may&#xD;
                  be eligible if they are able to be switched to an alternative therapy that is not&#xD;
                  a strong CYP3A4/5 inhibitor prior to registration on study&#xD;
&#xD;
          -  Patients with a history of allergic reactions attributed to compounds of similar&#xD;
             chemical or biologic composition to ibrutinib are not eligible&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness including, but not limited to, any of&#xD;
             the following are not eligible:&#xD;
&#xD;
               -  Ongoing or active systemic infection&#xD;
&#xD;
               -  Symptomatic congestive heart failure&#xD;
&#xD;
               -  Myocardial infarction within 6 months prior to registration&#xD;
&#xD;
               -  Unstable angina pectoris&#xD;
&#xD;
               -  Uncontrolled or symptomatic cardiac arrhythmias&#xD;
&#xD;
               -  Any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New&#xD;
                  York Heart Association Functional Classification&#xD;
&#xD;
               -  Psychiatric illness/social situations that would limit compliance with study&#xD;
                  requirements&#xD;
&#xD;
          -  Patients who have any life-threatening illness, medical condition, or organ system&#xD;
             dysfunction which, in the investigator's opinion, could compromise the subject's&#xD;
             safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the&#xD;
             study outcomes at risk are not eligible&#xD;
&#xD;
          -  Patients with a known human immunodeficiency virus (HIV) infection are not eligible&#xD;
             (HIV testing not required)&#xD;
&#xD;
          -  Patients with a known John Cunningham (JC) virus infection and/or progressive&#xD;
             multifocal leukoencephalopathy (PML) are not eligible&#xD;
&#xD;
          -  Patients with clinically active hepatitis A, B, or C infections are not eligible&#xD;
&#xD;
          -  Female patients who are pregnant and/or lactating are not eligible&#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>Barbara Pro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University- Lake Forest Hospital</name>
      <address>
        <city>Lake Forest</city>
        <state>Illinois</state>
        <zip>60045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tyrosine Protein Kinase Inhibitors</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/NCT02242097
org study id: NU 14H06
secondary id: NCI-2014-01777
secondary id: PCI-32765MCL2003
secondary id: STU00098385
secondary id: NU 14H06
secondary id: P30CA060553
nct id: NCT02242097
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study is being done to see whether or not a drug called ibrutinib can be given to
      patients with mantle cell lymphoma (MCL) as maintenance therapy after induction chemotherapy.
      This drug blocks an enzyme that affects how the lymphocytes grow and survive. The
      investigators hope to learn how safe and effective ibrutinib is for treating patients with
      MCL after responding to induction chemotherapy.
PRIMARY OBJECTIVES:

      I. To determine the progression-free survival (PFS) rate after 2 years.

      SECONDARY OBJECTIVES:

      I. Assess toxicity. II. Determine rates of conversion from partial response (PR) to complete
      response (CR).

      III. Determine median overall survival (OS) after 4 years.

      TERTIARY OBJECTIVES:

      I. Compare minimal residual disease (MRD) results overtime by polymerase chain reaction (PCR)
      and correlate these with PFS and OS.

      OUTLINE:

      Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28
      days for up to 4 years in the absence of disease progression, unacceptable toxicity or
      patient preference.

      After completion of study treatment, patients who completed 4 years of treatment are followed
      up at 30 days. Patients who did not complete 4 years of treatment are followed up for up to 4
      years post-first dose of treatment (every 3 months for 2 years and then every 6 months for 4
      years).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determine the progression-free survival (PFS) rate after 2 years
time frame: Assessed at 2 years
description: PFS will be measured from start of treatment to time of progression. Evidence of clinical progression will be documented by imaging (CT scan) for patients who have measurable disease.
measure: Incidence of adverse events, defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0
time frame: Up to 30 days after completion of study treatment, maximum 4 years post-first dose
description: To assess toxicity, all adverse events will be summarized as to type, severity, frequency, timing and attribution.
measure: Rate of conversion from Partial Response (PR) to Complete Response (CR)
time frame: Up to 4 years
description: Progression will be evaluated using Cheson 2007 criteria, only patients who had a PR at the time of registration and who complete ≥ 1 complete cycle of ibrutinib maintenance therapy will be evaluable for this endpoint.
measure: Determine median Overall Survival (OS) after 4 years
time frame: Up to 4 years post-first dose
description: Patients will be evaluated monthly for the first 6 months on treatment, then every 3 months thereafter. Patients who go off treatment will continue to be followed for up to 4 years post-first dose. Follow-up will occur every 3 months (up to 2 years after the first dose of treatment) and then every 6 months thereafter (up to 4 years post-first dose). Median OS after 4 years will be calculated.
measure: Compare Minimum Residual Disease (MRD) results overtime by Polymerase Chain Reaction (PCR) and correlate these with PFS and OS
time frame: Four time-points: baseline (pre-treatment), after 1 month and 6 months of treatment, and approximately 18-24 months post-first dose of treatment
description: Archived tissue from a previous biopsy from all patients will be obtained for baseline clone identification; in addition, peripheral whole blood samples will be collected at four time points. MRD analysis will be conducted using PCR methods and results will be compared over time and correlated with PFS and OS.
arm group label: Treatment (ibrutinib)
arm group type: Experimental
description: Patients receive ibrutinib orally PO QD on days 1-28. Courses repeat every 28 days for up to 4 years in the absence of disease progression, unacceptable toxicity, or patient preference.
intervention type: Drug
intervention name: ibrutinib
description: Given PO
arm group label: Treatment (ibrutinib)
other name: Bruton's tyrosine kinase inhibitor PCI-32765
other name: BTK inhibitor PCI-32765
other name: CRA-032765
other name: Imbruvica
other name: PCI-32765
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (ibrutinib)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Barbara Pro, MD
role: Principal Investigator
affiliation: Northwestern University
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Mantle-Cell
mesh term: Tyrosine Protein Kinase Inhibitors