<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/NCT03015896</url>
  </required_header>
  <id_info>
    <org_study_id>OSU-16167</org_study_id>
    <secondary_id>NCI-2016-01966</secondary_id>
    <nct_id>NCT03015896</nct_id>
  </id_info>
  <brief_title>Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma</brief_title>
  <official_title>A Phase I/II Study of the PD-1 Antibody Nivolumab in Combination With Lenalidomide in Relapsed/Refractory Non-Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>David Bond, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ohio State University Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This I/II trial studies the side effects and best dose of lenalidomide when given together&#xD;
      with nivolumab and to see how well they work in treating patients with non-Hodgkin or Hodgkin&#xD;
      lymphoma that has come back and does not respond to treatment. Monoclonal antibodies, such as&#xD;
      nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in&#xD;
      chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells,&#xD;
      either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving nivolumab and lenalidomide may work better in treating patients with&#xD;
      non-Hodgkin or Hodgkin lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the safety and tolerability of the combination of lenalidomide and nivolumab&#xD;
      in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). (Phase I) II. To determine&#xD;
      the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the combination of&#xD;
      lenalidomide and nivolumab in patients with relapsed/refractory NHL. (Phase I) III. To&#xD;
      evaluate the feasibility and toxicities of the combination of lenalidomide and nivolumab in&#xD;
      patients with relapsed/refractory Hodgkin's disease (HD). (Phase IB) IV. To evaluate the&#xD;
      efficacy of the combination of lenalidomide and nivolumab in terms of overall response rate&#xD;
      in patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell&#xD;
      lymphoma (DLBCL). (Phase II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the efficacy of the combination of lenalidomide and nivolumab in patients with&#xD;
      relapsed/refractory NHL in terms of overall response rate (ORR), duration of response (DOR),&#xD;
      progression-free survival (PFS) and overall survival (OS). (Phase I) II. To evaluate the&#xD;
      efficacy of the combination of lenalidomide and nivolumab in patients with&#xD;
      relapsed/refractory HD in terms of complete response rate (CR). (Phase IB) III. To evaluate&#xD;
      the efficacy of the combination of lenalidomide and nivolumab in patients with&#xD;
      relapsed/refractory HD in terms of duration of response (DOR), progression-free survival&#xD;
      (PFS) and overall survival (OS). (Phase IB) IV. To evaluate the efficacy of the combination&#xD;
      of lenalidomide and nivolumab in patients with relapsed/refractory FL and DLBCL in terms of&#xD;
      duration of response (DOR), progression-free survival (PFS) and overall survival (OS). (Phase&#xD;
      II)&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To explore the relationship between prognostic parameters including ki-67 staining, PD-1&#xD;
      staining and cell of origin (activated B-cell or ABC versus germinal center B-cell or GCB)&#xD;
      with ORR to the combination of lenalidomide and nivolumab in patients with&#xD;
      relapsed/refractory NHL. (Phase I) II. To evaluate and monitor effects on B-, T-, and natural&#xD;
      killer (NK)-cell function with the combination of lenalidomide and nivolumab in patients with&#xD;
      relapsed/refractory NHL. (Phase I) III. To explore the relationship between prognostic&#xD;
      parameters including ki-67 staining, PD-1 staining and cell of origin (activated B-cell or&#xD;
      ABC versus germinal center B-cell or GCB) with ORR to the combination of lenalidomide and&#xD;
      nivolumab in patients with relapsed/refractory FL and DLBCL. (Phase II) IV. To evaluate and&#xD;
      monitor effects on B-, T-, and NK-cell function with the combination of lenalidomide and&#xD;
      nivolumab in patients with relapsed/refractory FL and DLBCL. (Phase II)&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II&#xD;
      study.&#xD;
&#xD;
      Patients receive lenalidomide orally (PO) on days 1-21 and nivolumab intravenously (IV) over&#xD;
      60 minutes on days 1 and 15 of courses 1-4 and on day 1 of courses 5-12. Courses repeat every&#xD;
      28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 2 years,&#xD;
      then every 6 months for up to 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 14, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1/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>Incidence of adverse events summarized by NCI CTCAE version 4</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be assessed and tabulated across all patients who received any treatment with a focus on severe (grade 3+) adverse events and toxicities (ie those deemed at least possibly related to study treatment). Will also assess tolerability of the regimens through assessing the number of patients who required dose modifications and/or dose delays. Will capture the proportion of patients who go off treatment due to adverse events or those who refuse to continue treated for lesser toxicities.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) defined as the dose level at which no more than one of 6 patients experiences a dose-limiting toxicity summarized by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Will be assessed and tabulated across all patients who received any treatment with a focus on severe (grade 3+) adverse events and toxicities (ie those deemed at least possibly related to study treatment). Will also assess tolerability of the regimens through assessing the number of patients who required dose modifications and/or dose delays. Will capture the proportion of patients who go off treatment due to adverse events or those who refuse to continue treated for lesser toxicities.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete response rate (CR) in patients</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Complete response rate (CR) in patients with relapsed/refractory HD receiving the combination of lenalidomide and nivolumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Overall Response Rate in patients with relapsed/refractory HD receiving the combination of lenalidomide and nivolumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From study entry to the time of death due to any cause, assessed up to 5 years</time_frame>
    <description>Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From study entry to the time of progression and/or death, assessed up to 5 years</time_frame>
    <description>Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Grade 3a Follicular Lymphoma</condition>
  <condition>Recurrent Burkitt Lymphoma</condition>
  <condition>Recurrent Diffuse Large B-Cell Lymphoma</condition>
  <condition>Recurrent Follicular Lymphoma</condition>
  <condition>Recurrent Grade 1 Follicular Lymphoma</condition>
  <condition>Recurrent Grade 2 Follicular Lymphoma</condition>
  <condition>Recurrent Lymphoplasmacytic Lymphoma</condition>
  <condition>Recurrent Mantle Cell Lymphoma</condition>
  <condition>Recurrent Marginal Zone Lymphoma</condition>
  <condition>Recurrent Waldenstrom Macroglobulinemia</condition>
  <condition>Refractory Burkitt Lymphoma</condition>
  <condition>Refractory Diffuse Large B-Cell Lymphoma</condition>
  <condition>Refractory Follicular Lymphoma</condition>
  <condition>Refractory Lymphoplasmacytic Lymphoma</condition>
  <condition>Refractory Mantle Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (lenalidomide, nivolumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 60 minutes on days 1 and 15 of courses 1-4 and on day 1 of courses 5-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (lenalidomide, nivolumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (lenalidomide, nivolumab)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>CC5013</other_name>
    <other_name>CDC 501</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, nivolumab)</arm_group_label>
    <other_name>BMS-936558</other_name>
    <other_name>MDX-1106</other_name>
    <other_name>NIVO</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  PHASE I: Histologically confirmed B-cell NHL with any of the following subtypes:&#xD;
             DLBCL, mantle cell lymphoma (MCL), FL, marginal zone lymphoma (MZL) and&#xD;
             lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LL/WM), Burkitt's lymphoma&#xD;
             (BL); patients with histological transformation to DLBCL from indolent lymphoma,&#xD;
             primary mediastinal lymphoma and grey zone lymphoma are eligible&#xD;
&#xD;
          -  PHASE I: Histologically confirmed classical or lymphocyte predominant Hodgkin's&#xD;
             disease that is relapsed or refractory after at least one prior chemotherapy&#xD;
&#xD;
          -  PHASE I: Patients must have received at least one prior therapy; prior autologous stem&#xD;
             cell transplant is permitted; patients with DLBCL who have not had prior high-dose&#xD;
             therapy (HDT)/autologous stem cell transplant (ASCT) must be ineligible for&#xD;
             transplant; prior lenalidomide is not permitted if patients have progressed on therapy&#xD;
&#xD;
          -  PHASE IB DOSE EXPANSION: Histologically confirmed classical or lymphocyte predominant&#xD;
             Hodgkin's disease&#xD;
&#xD;
          -  PHASE IB DOSE EXPANSION: Patients must have received at least one prior therapy; prior&#xD;
             autologous stem cell transplant is permitted; patients who have not had prior HDT/ASCT&#xD;
             must be ineligible for transplant; prior lenalidomide is not permitted if patients&#xD;
             have progressed on therapy&#xD;
&#xD;
          -  PHASE II: Histologically confirmed B-cell NHL:&#xD;
&#xD;
               -  Cohort 1: with only de novo DLBCL or transformed indolent Non-Hodgkin's lymphoma&#xD;
                  (excludes Richter's syndrome).&#xD;
&#xD;
               -  Cohort 2: with only FL of grade 1, 2 or 3a&#xD;
&#xD;
          -  PHASE II: Patients must have received at least one prior therapy (in patients with&#xD;
             transformed DLBCL must have received at least one prior therapy; prior autologous stem&#xD;
             cell transplant is permitted; patients with DLBCL who have not had prior HDT/ASCT must&#xD;
             be ineligible for transplant; prior lenalidomide is not permitted if patients have&#xD;
             progressed on therapy&#xD;
&#xD;
          -  Be willing and able to provide written informed consent/assent for the trial&#xD;
&#xD;
          -  Have evaluable disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500 /mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000 /mcL in the absence of transfusion support within 7 days of&#xD;
             determining eligibility&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 g/dL&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 X upper limit of normal (ULN) OR measured or calculated&#xD;
             creatinine clearance (glomerular filtration rate [GFR] can also be used in place of&#xD;
             creatinine or creatinine clearance [CrCl]) &gt;= 40 mL/min creatinine clearance&#xD;
&#xD;
          -  Serum total bilirubin =&lt; 1.5 X ULN OR except subjects with Gilbert syndrome, who can&#xD;
             have total bilirubin &lt; 3.0 mg/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =&lt; 3.0 X&#xD;
             ULN&#xD;
&#xD;
          -  Female subject of childbearing potential should have a negative urine or serum&#xD;
             pregnancy at screening and within 24 hours prior to receiving the first dose of study&#xD;
             medication; if the urine test is positive or cannot be confirmed as negative, a serum&#xD;
             pregnancy test will be required&#xD;
&#xD;
          -  Female subjects of childbearing potential should be willing to use 2 methods of birth&#xD;
             control or be surgically sterile, or abstain from heterosexual activity for the course&#xD;
             of the study through 120 days after the last dose of study medication; subjects should&#xD;
             agree to ongoing pregnancy testing during the course of the study and after the end of&#xD;
             study therapy; female subjects of childbearing potential are those who have not been&#xD;
             surgically sterilized or have not been free from menses for &gt; 1 year&#xD;
&#xD;
          -  Male subjects should agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 120 days after the last dose of study therapy;&#xD;
             males must refrain from donating sperm during study participation and for 120 days&#xD;
             after the last dose of study medication&#xD;
&#xD;
          -  Willing and able to receive adequate prophylaxis and/or therapy for thromboembolic&#xD;
             events&#xD;
&#xD;
          -  Be willing and able to understand and give written informed consent and comply with&#xD;
             all study related procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigational&#xD;
             device within 3 weeks of the first dose of treatment&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment; subjects may use topical or inhaled corticosteroids or low-dose steroids&#xD;
             (=&lt; 20 mg of prednisone or equivalent per day) as therapy for comorbid conditions;&#xD;
             during study participation, subjects may receive systemic or enteric corticosteroids&#xD;
             as needed for treatment-emergent comorbid conditions&#xD;
&#xD;
          -  Has a known history of active TB (bacillus tuberculosis)&#xD;
&#xD;
          -  Hypersensitivity to nivolumab or lenalidomide or any of their excipients&#xD;
&#xD;
          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to study&#xD;
             day 1 or who has not recovered (i.e., =&lt; grade 1 or at baseline) from adverse events&#xD;
             due to agents administered more than 4 weeks earlier&#xD;
&#xD;
          -  Has had prior chemotherapy or radiation therapy within 2 weeks prior to study day 1 or&#xD;
             who has not recovered (i.e., =&lt; grade 1 or at baseline) from adverse events due to a&#xD;
             previously administered agent&#xD;
&#xD;
               -  Note: subjects with =&lt; grade 2 neuropathy are an exception to this criterion and&#xD;
                  may qualify for the study&#xD;
&#xD;
               -  Note: if subject received major surgery, they must have recovered adequately from&#xD;
                  the toxicity and/or complications from the intervention prior to starting&#xD;
                  therapy; patients must be 4 weeks out from major procedures&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment;&#xD;
             exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer&#xD;
&#xD;
          -  Has known active central nervous system (CNS) lymphoma&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs); replacement therapy (thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment; conditions expected to not recur in the absence of an&#xD;
             external trigger&#xD;
&#xD;
          -  Has an active infection requiring intravenous systemic therapy&#xD;
&#xD;
          -  Is unable to swallow capsules or malabsorption syndrome, disease or condition&#xD;
             significantly affecting gastrointestinal function&#xD;
&#xD;
          -  Clinically significant cardiovascular disease with uncontrolled arrhythmia, New York&#xD;
             Association class 3 or 4 congestive heart failure, history of myocardial infarction&#xD;
             within 6 months, or prolonged corrected QT (QTc) &gt; 500 msec&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment&#xD;
&#xD;
          -  Has progressed on prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent&#xD;
&#xD;
          -  Has progressed on prior therapy with lenalidomide&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)&#xD;
&#xD;
          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or&#xD;
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is&#xD;
             detected)&#xD;
&#xD;
          -  Has a history of deep venous thrombosis/embolism, threatening thromboembolism or known&#xD;
             thrombophilia or are at a high risk for a thromboembolic event in the opinion of the&#xD;
             investigator and who are not willing/able to take venous thromboembolic event&#xD;
             prophylaxis during the entire treatment period&#xD;
&#xD;
          -  Has a history of prior allogeneic hematopoietic cell transplant with a history of&#xD;
             prior Graft Versus Host Disease&#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 Bond, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://cancer.osu.edu</url>
    <description>The Jamesline</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>March 1, 2023</last_update_submitted>
  <last_update_submitted_qc>March 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University Comprehensive Cancer Center</investigator_affiliation>
    <investigator_full_name>David Bond, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Burkitt Lymphoma</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
  </intervention_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/NCT03015896
org study id: OSU-16167
secondary id: NCI-2016-01966
nct id: NCT03015896
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This I/II trial studies the side effects and best dose of lenalidomide when given together
      with nivolumab and to see how well they work in treating patients with non-Hodgkin or Hodgkin
      lymphoma that has come back and does not respond to treatment. Monoclonal antibodies, such as
      nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in
      chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving nivolumab and lenalidomide may work better in treating patients with
      non-Hodgkin or Hodgkin lymphoma.
PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of the combination of lenalidomide and nivolumab
      in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). (Phase I) II. To determine
      the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the combination of
      lenalidomide and nivolumab in patients with relapsed/refractory NHL. (Phase I) III. To
      evaluate the feasibility and toxicities of the combination of lenalidomide and nivolumab in
      patients with relapsed/refractory Hodgkin's disease (HD). (Phase IB) IV. To evaluate the
      efficacy of the combination of lenalidomide and nivolumab in terms of overall response rate
      in patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell
      lymphoma (DLBCL). (Phase II)

      SECONDARY OBJECTIVES:

      I. To evaluate the efficacy of the combination of lenalidomide and nivolumab in patients with
      relapsed/refractory NHL in terms of overall response rate (ORR), duration of response (DOR),
      progression-free survival (PFS) and overall survival (OS). (Phase I) II. To evaluate the
      efficacy of the combination of lenalidomide and nivolumab in patients with
      relapsed/refractory HD in terms of complete response rate (CR). (Phase IB) III. To evaluate
      the efficacy of the combination of lenalidomide and nivolumab in patients with
      relapsed/refractory HD in terms of duration of response (DOR), progression-free survival
      (PFS) and overall survival (OS). (Phase IB) IV. To evaluate the efficacy of the combination
      of lenalidomide and nivolumab in patients with relapsed/refractory FL and DLBCL in terms of
      duration of response (DOR), progression-free survival (PFS) and overall survival (OS). (Phase
      II)

      TERTIARY OBJECTIVES:

      I. To explore the relationship between prognostic parameters including ki-67 staining, PD-1
      staining and cell of origin (activated B-cell or ABC versus germinal center B-cell or GCB)
      with ORR to the combination of lenalidomide and nivolumab in patients with
      relapsed/refractory NHL. (Phase I) II. To evaluate and monitor effects on B-, T-, and natural
      killer (NK)-cell function with the combination of lenalidomide and nivolumab in patients with
      relapsed/refractory NHL. (Phase I) III. To explore the relationship between prognostic
      parameters including ki-67 staining, PD-1 staining and cell of origin (activated B-cell or
      ABC versus germinal center B-cell or GCB) with ORR to the combination of lenalidomide and
      nivolumab in patients with relapsed/refractory FL and DLBCL. (Phase II) IV. To evaluate and
      monitor effects on B-, T-, and NK-cell function with the combination of lenalidomide and
      nivolumab in patients with relapsed/refractory FL and DLBCL. (Phase II)

      OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II
      study.

      Patients receive lenalidomide orally (PO) on days 1-21 and nivolumab intravenously (IV) over
      60 minutes on days 1 and 15 of courses 1-4 and on day 1 of courses 5-12. Courses repeat every
      28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      then every 6 months for up to 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events summarized by NCI CTCAE version 4
time frame: Up to 5 years
description: Will be assessed and tabulated across all patients who received any treatment with a focus on severe (grade 3+) adverse events and toxicities (ie those deemed at least possibly related to study treatment). Will also assess tolerability of the regimens through assessing the number of patients who required dose modifications and/or dose delays. Will capture the proportion of patients who go off treatment due to adverse events or those who refuse to continue treated for lesser toxicities.
measure: Maximum tolerated dose (MTD) defined as the dose level at which no more than one of 6 patients experiences a dose-limiting toxicity summarized by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
time frame: Up to 28 days
description: Will be assessed and tabulated across all patients who received any treatment with a focus on severe (grade 3+) adverse events and toxicities (ie those deemed at least possibly related to study treatment). Will also assess tolerability of the regimens through assessing the number of patients who required dose modifications and/or dose delays. Will capture the proportion of patients who go off treatment due to adverse events or those who refuse to continue treated for lesser toxicities.
measure: Complete response rate (CR) in patients
time frame: Up to 5 years
description: Complete response rate (CR) in patients with relapsed/refractory HD receiving the combination of lenalidomide and nivolumab
measure: Overall Response Rate (ORR)
time frame: Up to 5 years
description: Overall Response Rate in patients with relapsed/refractory HD receiving the combination of lenalidomide and nivolumab
measure: Overall Survival (OS)
time frame: From study entry to the time of death due to any cause, assessed up to 5 years
description: Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.
measure: Progression free survival (PFS)
time frame: From study entry to the time of progression and/or death, assessed up to 5 years
description: Will be evaluated for each of the cohorts and graphically summarized using the methods of Kaplan and Meier.
arm group label: Treatment (lenalidomide, nivolumab)
arm group type: Experimental
description: Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 60 minutes on days 1 and 15 of courses 1-4 and on day 1 of courses 5-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (lenalidomide, nivolumab)
intervention type: Drug
intervention name: Lenalidomide
description: Given PO
arm group label: Treatment (lenalidomide, nivolumab)
other name: CC-5013
other name: CC5013
other name: CDC 501
other name: Revlimid
intervention type: Biological
intervention name: Nivolumab
description: Given IV
arm group label: Treatment (lenalidomide, nivolumab)
other name: BMS-936558
other name: MDX-1106
other name: NIVO
other name: ONO-4538
other name: Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Bond, MD
role: Principal Investigator
affiliation: Ohio State University Comprehensive Cancer Center
facility: 
facility: 
country: United States
url: http://cancer.osu.edu
description: The Jamesline
responsible party type: Sponsor-Investigator
investigator affiliation: Ohio State University Comprehensive Cancer Center
investigator full name: David Bond, MD
investigator title: Principal Investigator
mesh term: Burkitt Lymphoma
mesh term: Lymphoma
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Waldenstrom Macroglobulinemia
mesh term: Recurrence
mesh term: Nivolumab
mesh term: Lenalidomide
sharing ipd: No