<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/NCT01732861</url>
  </required_header>
  <id_info>
    <org_study_id>CC-292-CLL-001</org_study_id>
    <secondary_id>2012-003766-41</secondary_id>
    <nct_id>NCT01732861</nct_id>
  </id_info>
  <brief_title>Safety Study of CC-292 and Lenalidomide in Subjects With Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma</brief_title>
  <official_title>A MULTICENTER, PHASE 1B, OPEN-LABEL STUDY TO DETERMINE THE SAFETY AND ACTIVITY OF CC-292 IN COMBINATION WITH LENALIDOMIDE IN SUBJECTS WITH RELAPSED AND/OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA / SMALL LYMPHOCYTIC LYMPHOMA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a dose finding study using a 3 + 3 dose escalation and expansion design to determine&#xD;
      a Not Tolerated Dose (NTD), Optimal Biological Effect Dose (OBE) and / or Maximum Tolerated&#xD;
      Dose (MTD). These data will be used to establish a Recommended Phase 2 Dose (RP2D) for the&#xD;
      combination of CC-292 and lenalidomide in subjects with Chronic Lymphocytic Leukemia (CLL).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This dose finding study uses a 3 + 3 dose escalation and expansion design to establish the&#xD;
      recommended Phase 2 dose. The starting dose is CC-292 375 mg twice daily and Lenalidomide 10&#xD;
      mg once daily. After review of the data for dose limiting toxicities (DLTs), the second dose&#xD;
      level will be enrolled. Doses for this second cohort are CC-292 500 mg twice daily and&#xD;
      lenalidomide 10 mg once daily. Additional doses of lenalidomide in combination with CC-292&#xD;
      may be evaluated to accurately determine the maximum tolerated dose. Once the maximum&#xD;
      tolerated dose and/or optimal biologic effect has been ascertained, an expansion cohort of 24&#xD;
      subjects may be enrolled.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 28, 2012</start_date>
  <completion_date type="Actual">January 23, 2019</completion_date>
  <primary_completion_date type="Actual">January 23, 2019</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>Adverse Events</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Number of participants with adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Have Received Some Form of Response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Response rate is defined as the percentage of participants who have achieved some form of response including: a Complete Response (CR), a CR with incomplete bone marrow recovery, a Nodular Partial Response (PR), a Nodal PR or a PR with lymphoctyosis) based on the International Workshop for Chronic Lymphocytic Leukemia and lymphoma guidelines (IWCLL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK-Cmax</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>Maximum observed plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK-Tmax</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>Time to maximum observed plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK-λz</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear plasma concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK-t1/2</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>Estimate of the terminal elimination half-life in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK-AUC (0-t)</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK-AUC0-∞</measure>
    <time_frame>Up to 15 days</time_frame>
    <description>Area under the plasma concentration time curve from time zero extrapolated to infinity.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Leukemia Lymphocytic Chronic B-Cell</condition>
  <arm_group>
    <arm_group_label>CC-292 + Lenalidomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CC-292</intervention_name>
    <description>CC-292-will be given twice daily on Days 8-28 of Cycle 1 and on Days 1-28 of the remaining 28-day cycles.</description>
    <arm_group_label>CC-292 + Lenalidomide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Lenalidomde will be given once daily on Days 1-28 of 28-day cycles.</description>
    <arm_group_label>CC-292 + Lenalidomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects 18 years of age and older at the time of signing the informed&#xD;
             consent document (ICD).&#xD;
&#xD;
          -  Body weight at least 50 kg.&#xD;
&#xD;
          -  Must have a documented diagnosis of CLL/SLL (International Workshop on Chronic&#xD;
             Lymphocytic Leukemia IWCLL Guidelines - Hallek 2008) by investigator assessment.&#xD;
&#xD;
          -  Have failed at least 1 previous treatments for CLL/SLL, and have relapsed and/or&#xD;
             refractory disease following last prior treatment defined as CLL/SLL that does not&#xD;
             achieve at least a partial response (PR) to therapy or that progresses within 6 months&#xD;
             of treatment.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or less.&#xD;
&#xD;
          -  Life expectancy of at least 3 months from time of signing ICD.&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must have a negative medically supervised&#xD;
             pregnancy test prior to starting study therapy and agree to ongoing pregnancy testing&#xD;
             during and after end of study therapy; commit to continued abstinence from&#xD;
             heterosexual intercourse or agree to use, comply with two effective methods of&#xD;
             contraception without interruption, 28 days prior to starting study drug, during study&#xD;
             therapy, and for 28 days after discontinuation of study therapy.&#xD;
&#xD;
          -  Male subjects must agree to use a latex condom during sexual contact with a FCBP even&#xD;
             if they have had a vasectomy, throughout study drug therapy and dose interruption, and&#xD;
             for 28 days after end of study therapy; agree to not donate semen or sperm during&#xD;
             study drug therapy and for 28 days after end of study drug therapy.&#xD;
&#xD;
          -  All subjects must understand that lenalidomide could have a potential teratogenic&#xD;
             risk, agree to abstain from donating blood with taking lenalidomide therapy and&#xD;
             following discontinuation of study drug therapy; have an echocardiogram (ECG) or&#xD;
             multigated acquisition (MUGA) scan of the heart demonstrating left ventricular&#xD;
             ejection fraction (LVEF) at least 50% or the institution's lower limit of normal; have&#xD;
             recovered from adverse, toxic effects of prior therapies to equal to or less than 1&#xD;
             (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events&#xD;
             [CTCAE] version 4.03 except for alopecia and peripheral neuropathy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Any significant medical condition, laboratory abnormality, or psychiatric illness that&#xD;
        would prevent the subject from participating in the study.&#xD;
&#xD;
          -  Autologous stem cell transplant within 3 months prior to the time of signature on the&#xD;
             ICD Informed Consent Document.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection requiring parenteral antibiotics; uncontrolled diabetes mellitus; chronic&#xD;
             symptomatic congestive heart failure; unstable angina pectoris, angioplasty, stenting,&#xD;
             or myocardial infarctions within 6 months prior to the time of signature on the ICD;&#xD;
             clinically significant cardiac arrhythmia that is symptomatic or requires treatment,&#xD;
             or asymptomatic sustained ventricular tachycardia. Subjects with controlled atrial&#xD;
             fibrillation that is asymptomatic are eligible.&#xD;
&#xD;
          -  Pregnant or lactating females.&#xD;
&#xD;
          -  Prior history of malignancies, unless the subject has been free of the disease for 5&#xD;
             years or more prior to the time of signature on the ICD. Exceptions to the 5 years or&#xD;
             more time limit include history of basal cell carcinoma of the skin; squamous cell&#xD;
             carcinoma of the skin; carcinoma in situ of the cervix; carcinoma in situ of the&#xD;
             breast; carcinoma in situ of the bladder; incidental histologic finding of prostate&#xD;
             cancer (Tumor/Nodes/Metastasis [TNM] stage of T1a or T1b).&#xD;
&#xD;
          -  Known seropositivity for or history of active viral infection with human&#xD;
             immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Known seropositivity for hepatitis C virus (HCV); hepatitis B virus (HBV).&#xD;
&#xD;
          -  Subjects who are at a high risk for a thromboembolic event and are not willing/able to&#xD;
             take venous thromboembolic event (VTE) prophylaxis.&#xD;
&#xD;
          -  Any of the following laboratory abnormalities:&#xD;
&#xD;
               1. Absolute Neutrophil Count (ANC) ≤ 1,000 cells/mm3 (1.0 x 109/L)&#xD;
&#xD;
               2. Platelet count ≤ 50,000/mm3 (50 x 109/L) unless secondary to bone marrow&#xD;
                  involvement by recent bone marrow aspiration and bone marrow biopsy&#xD;
&#xD;
               3. Serum Aspartate Transaminase/Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT)&#xD;
                  or Alanine Transaminase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) &gt; 3.0 x&#xD;
                  upper limit of normal (ULN) or &gt; 5.0 x ULN in cases of documented liver&#xD;
                  involvement&#xD;
&#xD;
               4. Serum bilirubin &gt; 1.5 x ULN or &gt; 3.0 x ULN in cases of Gilbert's Syndrome and&#xD;
                  documented liver involvement by lymphoma;&#xD;
&#xD;
               5. Calculated creatinine clearance using the Cockcroft-Gault formula&#xD;
                  (Cockcroft,1976)&#xD;
&#xD;
               6. Corrected QT interval (QTc) prolongation (defined as a QTc &gt; 450 msec for males&#xD;
                  and &gt; 470 msec for females [Fridericia's correction]) or other clinically&#xD;
                  significant ECG abnormalities as assessed by the investigator.&#xD;
&#xD;
          -  Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within&#xD;
             28 days of Day 1 dosing.&#xD;
&#xD;
          -  Use of systemic corticosteroids in doses greater than prednisone equivalent to 20&#xD;
             mg/day within 3 weeks prior to study drug dosing.&#xD;
&#xD;
          -  Concomitant use of medicines known to cause QT prolongation or torsades de pointes.&#xD;
&#xD;
          -  Chronic use of H2 antagonists or proton pump inhibitors or their use within 7 days of&#xD;
             first dose.&#xD;
&#xD;
          -  Gastrointestinal abnormalities including the inability to take oral medication,&#xD;
             requiring intravenous alimentation, or prior surgical procedure affecting absorption.&#xD;
&#xD;
          -  Prior treatment with Btk (Bruton's tyrosine kinase) inhibitors.&#xD;
&#xD;
          -  Any live vaccinations within 3 weeks from first dose.&#xD;
&#xD;
          -  History of hypersensitivity to immunomodulatory drugs (IMiDs) (eg, lenalidomide,&#xD;
             thalidomide, pomalidomide).&#xD;
&#xD;
          -  Disease transformation (ie, Richter's Syndrome [lymphomas] or prolymphocytic&#xD;
             leukemia).&#xD;
&#xD;
          -  Patients with uncontrolled hyper or hypothyroidism.&#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>David Liu, MD</last_name>
    <role>Study Director</role>
    <affiliation>Celgene</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clearview Cancer Institute Oncology Specialties, P.C</name>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <zip>35805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizon Oncology Center</name>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <zip>47905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai School of Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The West Clinic</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinik fur Innere Medizin</name>
      <address>
        <city>Innsbruck</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AKh Linz</name>
      <address>
        <city>Linz</city>
        <zip>4021</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinik der PMU</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allgemeines Krankenhaus Wien</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Abteilung-Zentrum fur Onkologie und Hamatologie</name>
      <address>
        <city>Wien</city>
        <zip>1100</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <last_update_submitted>December 19, 2019</last_update_submitted>
  <last_update_submitted_qc>December 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Lymphocytic Leukemia</keyword>
  <keyword>Small Lymphocytic Leukemia</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>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/NCT01732861
org study id: CC-292-CLL-001
secondary id: 2012-003766-41
nct id: NCT01732861
lead sponsor: 
has dmc: No
This is a dose finding study using a 3 + 3 dose escalation and expansion design to determine
      a Not Tolerated Dose (NTD), Optimal Biological Effect Dose (OBE) and / or Maximum Tolerated
      Dose (MTD). These data will be used to establish a Recommended Phase 2 Dose (RP2D) for the
      combination of CC-292 and lenalidomide in subjects with Chronic Lymphocytic Leukemia (CLL).
This dose finding study uses a 3 + 3 dose escalation and expansion design to establish the
      recommended Phase 2 dose. The starting dose is CC-292 375 mg twice daily and Lenalidomide 10
      mg once daily. After review of the data for dose limiting toxicities (DLTs), the second dose
      level will be enrolled. Doses for this second cohort are CC-292 500 mg twice daily and
      lenalidomide 10 mg once daily. Additional doses of lenalidomide in combination with CC-292
      may be evaluated to accurately determine the maximum tolerated dose. Once the maximum
      tolerated dose and/or optimal biologic effect has been ascertained, an expansion cohort of 24
      subjects may be enrolled.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: Up to 5 years
description: Number of participants with adverse events
measure: Percentage of Participants Who Have Received Some Form of Response
time frame: Up to 2 years
description: Response rate is defined as the percentage of participants who have achieved some form of response including: a Complete Response (CR), a CR with incomplete bone marrow recovery, a Nodular Partial Response (PR), a Nodal PR or a PR with lymphoctyosis) based on the International Workshop for Chronic Lymphocytic Leukemia and lymphoma guidelines (IWCLL).
measure: PK-Cmax
time frame: Up to 15 days
description: Maximum observed plasma concentration
measure: PK-Tmax
time frame: Up to 15 days
description: Time to maximum observed plasma concentration
measure: PK-λz
time frame: Up to 15 days
description: Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear plasma concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration
measure: PK-t1/2
time frame: Up to 15 days
description: Estimate of the terminal elimination half-life in plasma
measure: PK-AUC (0-t)
time frame: Up to 15 days
description: Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point
measure: PK-AUC0-∞
time frame: Up to 15 days
description: Area under the plasma concentration time curve from time zero extrapolated to infinity.
arm group label: CC-292 + Lenalidomide
arm group type: Experimental
intervention type: Drug
intervention name: CC-292
description: CC-292-will be given twice daily on Days 8-28 of Cycle 1 and on Days 1-28 of the remaining 28-day cycles.
arm group label: CC-292 + Lenalidomide
intervention type: Drug
intervention name: Lenalidomide
description: Lenalidomde will be given once daily on Days 1-28 of 28-day cycles.
arm group label: CC-292 + Lenalidomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Liu, MD
role: Study Director
affiliation: Celgene
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: United States
country: Germany
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lenalidomide