<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/NCT02200848</url>
  </required_header>
  <id_info>
    <org_study_id>NCI#9540</org_study_id>
    <nct_id>NCT02200848</nct_id>
  </id_info>
  <brief_title>Phase I Study of Lenalidomide, Rituximab and Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)</brief_title>
  <official_title>A Phase I Study of Lenalidomide in Combination With Rituximab and Ibrutinib in Relapsed and Refractory CLL and SLL</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Georgetown University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Georgetown University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is for subjects diagnosed with recurrent or relapsed CLL/SLL. The purpose of this&#xD;
      study is to test the safety of the combination of the drugs lenalidomide and ibrutinib at&#xD;
      different dose levels, in combination with the drug rituximab. We want to find out what&#xD;
      effects, good and/or bad, they have on patients with CLL/SLL.&#xD;
&#xD;
      The hypothesis of the study is that it will be safe to give the three drugs in combination&#xD;
      and the information learned from this trial will be used to study the 3 drug combination is a&#xD;
      larger future trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment consists of dose escalations of lenalidomide and ibrutinib and fixed doses of&#xD;
      rituximab. A small expansion cohort to include 10 patients will follow once the recommended&#xD;
      phase II dose is found.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment difficulties and toxicity&#xD;
  </why_stopped>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">August 1, 2017</completion_date>
  <primary_completion_date type="Actual">March 27, 2017</primary_completion_date>
  <phase>Phase 1</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>Recommended Phase II dose</measure>
    <time_frame>1year</time_frame>
    <description>The dose at which less than 2 of 6 patients experience a dose limiting toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>2 years</time_frame>
    <description>adverse events, serious adverse events, adverse events leading to discontinuation, deaths</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor efficacy</measure>
    <time_frame>2 years</time_frame>
    <description>Proportion of patients who achieve stable disease, partial or complete response; progression-free survival defined as duration of time from start of treatment to time of progression or death</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>Lenalidomide, Ibrutinib, Rituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rituximab on day 1, lenalidomide days 1-21 and ibrutinib continuously for 6 cycles or until disease progression or intolerance to the combination. Single agent ibrutinib will then be continued until disease progression or intolerance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide, Ibrutinib, Rituximab</intervention_name>
    <description>Dose level -2 Ibrutinib 280 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level -1 Ibrutinib 420 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level 1 Ibrutinib 420 mg; Lenalidomide 5 mg; Rituximab 375 mg/m2 Level 2 Ibrutinib 420 mg; Lenalidomide 10 mg; Rituximab 375 mg/m2 Level 3 Ibrutinib 420 mg; Lenalidomide 15 mg; Rituximab 375 mg/m2</description>
    <arm_group_label>Lenalidomide, Ibrutinib, Rituximab</arm_group_label>
    <other_name>Ibrutinib</other_name>
    <other_name>PCI-32765</other_name>
    <other_name>NSC# 748645</other_name>
    <other_name>Imbruvica</other_name>
    <other_name>Lenalidomide</other_name>
    <other_name>alpha-[3-aminophthalimido] glutarimide</other_name>
    <other_name>Revlimid</other_name>
    <other_name>CC-5013</other_name>
    <other_name>NSC#703813</other_name>
    <other_name>Rituximab</other_name>
    <other_name>IDEC-C2B8</other_name>
    <other_name>Rituxan</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma that&#xD;
             requires treatment&#xD;
&#xD;
          -  No prior systemic treatment within 4 weeks of enrollment&#xD;
&#xD;
          -  No corticosteroids within 2 weeks prior to study entry&#xD;
&#xD;
          -  Measurable disease must be present&#xD;
&#xD;
          -  No concomitant anti-cancer therapies&#xD;
&#xD;
          -  ECOG status &lt;/= 2&#xD;
&#xD;
          -  Patients with HIV infection are eligible&#xD;
&#xD;
          -  Patients with treated CLL or SLL in CNS are eligible&#xD;
&#xD;
          -  Non-pregnant and non-nursing&#xD;
&#xD;
          -  Life expectancy greater than 60 days&#xD;
&#xD;
          -  Adequate bone marrow, kidney and liver function&#xD;
&#xD;
          -  No major surgery within 28 days or minor surgery within 5 days of starting treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History od Richter's transformation&#xD;
&#xD;
          -  History of prior allogeneic transplant&#xD;
&#xD;
          -  Radioimmunotherapy within 1 year of enrollment&#xD;
&#xD;
          -  Prior Bruton's tyrosine kinase inhibitor or lenalidomide&#xD;
&#xD;
          -  History of allergic reactions to compounds similar to ibrutinib, lenalidomide or&#xD;
             rituximab or hypersensitivity&#xD;
&#xD;
          -  active or uncontrolled autoimmune hemolytic anemia or ITP&#xD;
&#xD;
          -  Transfusion-dependent thrombocytopenia or bleeding disorders&#xD;
&#xD;
          -  Active hepatitis B or C infections&#xD;
&#xD;
          -  History of known Human Anti-Chimeric Antibody positivity&#xD;
&#xD;
          -  History of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson&#xD;
             syndrome&#xD;
&#xD;
          -  History of uncontrolled seizures&#xD;
&#xD;
          -  Autoimmune disorder that requires active immunosuppression&#xD;
&#xD;
          -  Stroke or intracranial hemorrhage within last 6 months&#xD;
&#xD;
          -  History of congestive heart failure, myocardial infarction, unstable angina,&#xD;
             uncontrolled arrhythmia or any Class 3 or 4 heart disease in the last 6 months&#xD;
&#xD;
          -  No prior malignancy except if treated with curative intent with no active disease for&#xD;
             more than 3 years; adequately treated non-melanoma skin cancer or cervical cancer in&#xD;
             situ&#xD;
&#xD;
          -  using warfarin or similar Vitamin K antagonists Unable to swallow capsules or disease&#xD;
             significantly affecting gastrointestinal function or inhibiting small intestine&#xD;
             absorption&#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>Chaitra Ujjani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgetown Lombardi Comprehsnive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Georgetown Lombardi Comprehensive Cancer Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>January 10, 2018</last_update_submitted>
  <last_update_submitted_qc>January 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lenalidomide</keyword>
  <keyword>Ibrutinib</keyword>
  <keyword>Rituximab</keyword>
  <keyword>CLL</keyword>
  <keyword>SLL</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Glutarimide</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/NCT02200848
org study id: NCI#9540
nct id: NCT02200848
lead sponsor: 
collaborator: 
has dmc: Yes
This study is for subjects diagnosed with recurrent or relapsed CLL/SLL. The purpose of this
      study is to test the safety of the combination of the drugs lenalidomide and ibrutinib at
      different dose levels, in combination with the drug rituximab. We want to find out what
      effects, good and/or bad, they have on patients with CLL/SLL.

      The hypothesis of the study is that it will be safe to give the three drugs in combination
      and the information learned from this trial will be used to study the 3 drug combination is a
      larger future trial.
Treatment consists of dose escalations of lenalidomide and ibrutinib and fixed doses of
      rituximab. A small expansion cohort to include 10 patients will follow once the recommended
      phase II dose is found.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended Phase II dose
time frame: 1year
description: The dose at which less than 2 of 6 patients experience a dose limiting toxicity
measure: Safety
time frame: 2 years
description: adverse events, serious adverse events, adverse events leading to discontinuation, deaths
measure: Antitumor efficacy
time frame: 2 years
description: Proportion of patients who achieve stable disease, partial or complete response; progression-free survival defined as duration of time from start of treatment to time of progression or death
arm group label: Lenalidomide, Ibrutinib, Rituximab
arm group type: Experimental
description: Rituximab on day 1, lenalidomide days 1-21 and ibrutinib continuously for 6 cycles or until disease progression or intolerance to the combination. Single agent ibrutinib will then be continued until disease progression or intolerance.
intervention type: Drug
intervention name: Lenalidomide, Ibrutinib, Rituximab
description: Dose level -2 Ibrutinib 280 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level -1 Ibrutinib 420 mg; Lenalidomide 2.5 mg; Rituximab 375 mg/m2 Level 1 Ibrutinib 420 mg; Lenalidomide 5 mg; Rituximab 375 mg/m2 Level 2 Ibrutinib 420 mg; Lenalidomide 10 mg; Rituximab 375 mg/m2 Level 3 Ibrutinib 420 mg; Lenalidomide 15 mg; Rituximab 375 mg/m2
arm group label: Lenalidomide, Ibrutinib, Rituximab
other name: Ibrutinib
other name: PCI-32765
other name: NSC# 748645
other name: Imbruvica
other name: Lenalidomide
other name: alpha-[3-aminophthalimido] glutarimide
other name: Revlimid
other name: CC-5013
other name: NSC#703813
other name: Rituximab
other name: IDEC-C2B8
other name: Rituxan
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chaitra Ujjani, MD
role: Principal Investigator
affiliation: Georgetown Lombardi Comprehsnive Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Rituximab
mesh term: Lenalidomide
mesh term: Glutarimide