<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/NCT02207062</url>
  </required_header>
  <id_info>
    <org_study_id>9107</org_study_id>
    <secondary_id>NCI-2014-01573</secondary_id>
    <secondary_id>9107</secondary_id>
    <secondary_id>RG1714041</secondary_id>
    <nct_id>NCT02207062</nct_id>
  </id_info>
  <brief_title>Ibrutinib in Treating Patients With Relapsed or Refractory Transformed Indolent B-cell Non-Hodgkin Lymphoma</brief_title>
  <official_title>A Pilot Study of Single-Agent Ibrutinib in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot phase II trial studies ibrutinib in treating patients with transformed indolent (a&#xD;
      type of cancer that grows slowly) B-cell non-Hodgkin lymphoma that have returned after a&#xD;
      period of improvement (relapsed) or do not respond to treatment (refractory). Ibrutinib may&#xD;
      stop the growth of cancer cells by blocking some of the enzymes (proteins) needed for cell&#xD;
      growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      Patients receive ibrutinib orally (PO) once daily (QD) in the absence of disease progression&#xD;
      or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for up to 5&#xD;
      years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">November 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2023</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>Overall response rate (combined complete response + partial response)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete response rate</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Time from first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years</time_frame>
    <description>Progression-free survival will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate relative to the underlying B-cell histology</measure>
    <time_frame>Up to 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability of chronic ibrutinib therapy</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to classify and grade toxicities.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Recurrent Transformed B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Transformed B-Cell Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (ibrutinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity.</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>BTK Inhibitor PCI-32765</other_name>
    <other_name>CRA-032765</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 transformed indolent B-cell non-Hodgkin&#xD;
             lymphoma that is relapsed or refractory to at least one line of therapy&#xD;
&#xD;
          -  Patients must have a computed tomography (CT) (preferred) or magnetic resonance&#xD;
             imaging (MRI) scan of the chest, abdomen, and pelvis within 28 days of enrollment&#xD;
&#xD;
          -  Patients must have measurable disease defined as lesions greater than 1.5 cm that can&#xD;
             be accurately measured in two dimensions by CT (preferred), or MRI&#xD;
&#xD;
          -  Patients must have a positron emission tomography (PET) scan within 56 days of&#xD;
             enrollment&#xD;
&#xD;
          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0 to 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/mm^3 or &gt;= 750/mm^3 in the setting of marrow&#xD;
             involvement by disease&#xD;
&#xD;
          -  Platelets &gt;= 50,000/mm^3 or &gt;= 30,000/mm^3 in the setting of marrow involvement by&#xD;
             disease or splenomegaly due to disease&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x upper limit&#xD;
             of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of&#xD;
             non-hepatic origin&#xD;
&#xD;
          -  Creatinine clearance (Clcr) &gt; 25 mL/min&#xD;
&#xD;
          -  Patients must be anticipated to complete 2 cycles of therapy in the opinion of the&#xD;
             treating physician&#xD;
&#xD;
          -  Women of childbearing potential and men who are sexually active must affirm they are&#xD;
             practicing a highly effective method of birth control during and after the study&#xD;
             consistent with local regulations regarding the use of birth control methods for&#xD;
             subjects participating in clinical trials; men must agree to not donate sperm during&#xD;
             or after the study; for females, these restrictions apply for 1 month after the last&#xD;
             dose of study drug; for males, these restrictions apply for 3 months after the last&#xD;
             dose of the study drug&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum (beta-human chorionic&#xD;
             gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant&#xD;
             or breastfeeding are ineligible for this study&#xD;
&#xD;
          -  Sign (or their legally-acceptable representatives must sign) an informed consent&#xD;
             document in accordance with institutional and federal guidelines indicating that they&#xD;
             understand the investigational nature of and procedures required for the study,&#xD;
             including biomarkers, and are willing to participate in and comply with the guidelines&#xD;
             of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or&#xD;
             active hepatitis B virus infection or any uncontrolled active systemic infection&#xD;
&#xD;
          -  Major surgery or a wound that has not fully healed within 4 weeks of initiation of&#xD;
             therapy&#xD;
&#xD;
          -  Known central nervous system lymphoma&#xD;
&#xD;
          -  History of stroke or intracranial hemorrhage within 6 months of screening&#xD;
&#xD;
          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.,&#xD;
             phenprocoumon)&#xD;
&#xD;
          -  Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A)&#xD;
             inhibitors&#xD;
&#xD;
          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic&#xD;
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of&#xD;
             screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by&#xD;
             the New York Heart Association Functional Classification&#xD;
&#xD;
          -  Vaccinated with live, attenuated vaccines within 4 weeks of initiation of therapy&#xD;
&#xD;
          -  Any life-threatening illness, medical condition, or organ system dysfunction which, in&#xD;
             the investigator's opinion, could compromise the subject's safety, interfere with the&#xD;
             absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue&#xD;
             risk&#xD;
&#xD;
          -  Patients with other prior malignancies except for adequately treated basal cell&#xD;
             carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or&#xD;
             other cancer from which the patient has been disease-free for 5 years or greater,&#xD;
             unless approved by the protocol sponsor-investigator/lead-sub-investigator&#xD;
&#xD;
          -  Patients that previously were treated with ibrutinib for &gt; 7 days&#xD;
&#xD;
          -  Previous chemotherapy, immunotherapy, biologically targeted therapy, other&#xD;
             investigational agent, or radiation therapy within 3 weeks of initiation of ibrutinib&#xD;
             therapy or radio-immunotherapy within 12 weeks of initiation of ibrutinib therapy&#xD;
&#xD;
          -  Prior allogeneic transplant with graft-versus-host disease (GVHD) requiring&#xD;
             immunosuppressive therapy&#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>Ajay K. Gopal</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-Hodgkin Lymphoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02207062
org study id: 9107
secondary id: NCI-2014-01573
secondary id: 9107
secondary id: RG1714041
nct id: NCT02207062
lead sponsor: 
collaborator: 
has dmc: No
This pilot phase II trial studies ibrutinib in treating patients with transformed indolent (a
      type of cancer that grows slowly) B-cell non-Hodgkin lymphoma that have returned after a
      period of improvement (relapsed) or do not respond to treatment (refractory). Ibrutinib may
      stop the growth of cancer cells by blocking some of the enzymes (proteins) needed for cell
      growth.
OUTLINE:

      Patients receive ibrutinib orally (PO) once daily (QD) in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for up to 5
      years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate (combined complete response + partial response)
time frame: Up to 5 years
measure: Complete response rate
time frame: Up to 5 years
measure: Disease control rate
time frame: Up to 5 years
measure: Overall survival
time frame: Up to 5 years
measure: Progression-free survival
time frame: Time from first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
description: Progression-free survival will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).
measure: Response rate relative to the underlying B-cell histology
time frame: Up to 5 years
measure: Tolerability of chronic ibrutinib therapy
time frame: Up to 5 years
description: The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to classify and grade toxicities.
arm group label: Treatment (ibrutinib)
arm group type: Experimental
description: Patients receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Ibrutinib
description: Given PO
arm group label: Treatment (ibrutinib)
other name: BTK Inhibitor PCI-32765
other name: CRA-032765
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: Ajay K. Gopal
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
sharing ipd: No