<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/NCT02213913</url>
  </required_header>
  <id_info>
    <org_study_id>13-1406</org_study_id>
    <secondary_id>NCI-2014-01581</secondary_id>
    <secondary_id>IRB13-1406</secondary_id>
    <secondary_id>13-1406</secondary_id>
    <secondary_id>P30CA014599</secondary_id>
    <nct_id>NCT02213913</nct_id>
  </id_info>
  <brief_title>Lenalidomide and Combination Chemotherapy (DA-EPOCH-R) in Treating Patients With MYC-Associated B-Cell Lymphomas</brief_title>
  <official_title>Prospective, Multi-center Phase I/II Trial of Lenalidomide and Dose-Adjusted EPOCH-R in MYC-Associated B-Cell Lymphomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Chicago</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies the side effects and best dose of lenalidomide when given&#xD;
      together with combination chemotherapy and to see how well they work in treating patients&#xD;
      with v-myc myelocytomatosis viral oncogene homolog (avian) (MYC)-associated B-cell lymphomas.&#xD;
      Lenalidomide may stop the growth of B-cell lymphomas by blocking the growth of new blood&#xD;
      vessels necessary for cancer growth and by blocking some of the enzymes needed for cell&#xD;
      growth. Biological therapies, such as lenalidomide, use substances made from living organisms&#xD;
      that may stimulate or suppress the immune system in different ways and stop cancer cells from&#xD;
      growing. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate,&#xD;
      doxorubicin hydrochloride, cyclophosphamide, work in different ways to stop the growth of&#xD;
      cancer cells, either by killing the cells, by stopping them from dividing, or by stopping&#xD;
      them from spreading. Monoclonal antibodies, such as rituximab, may block cancer growth in&#xD;
      different ways by targeting certain cells. Giving lenalidomide together with combination&#xD;
      chemotherapy may be an effective treatment in patients with B-cell lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (MTD) of lenalidomide when added to dose-adjusted&#xD;
      (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide,&#xD;
      rituximab (EPOCH-R) (hereby termed &quot;DA-EPOCH-RR&quot;) in patients with double hit lymphoma (DHL)&#xD;
      lymphomas. (Phase I) II. To determine the 1- and 2-year progression free survival (PFS) of&#xD;
      DA-EPOCH-RR in patients with DHL lymphomas. (Phase II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Overall response rate, complete response, and duration of response. II. Quality of life&#xD;
      (QOL) measures using standardized scales. III. Toxicity assessment using version 4.0 of the&#xD;
      National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE)&#xD;
      criteria.&#xD;
&#xD;
      IV. Overall survival (OS) at 1 and 2 years.&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II&#xD;
      study.&#xD;
&#xD;
      INDUCTION PHASE: Patients receive lenalidomide orally (PO) daily on days 1-14. Treatment&#xD;
      repeats every 21 days for 6 courses in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      DA-EPOCH-R: Patients receive etoposide intravenously (IV) continuously on days 1-4,&#xD;
      prednisone PO twice daily (BID) on days 1-5, vincristine sulfate IV continuously on days 1-4,&#xD;
      doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on&#xD;
      day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment&#xD;
      repeats every 21 days for 6 courses in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      CONSOLIDATION PHASE: Patients who are transplantation (hematopoietic stem cell transplant&#xD;
      [HSCT])-eligible receive BCNU, etoposide, cytarabine, and melphalan (BEAM)-conditioning&#xD;
      regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating&#xD;
      physician. Patients who do not undergo HSCT in first remission receive lenalidomide&#xD;
      maintenance for 12 months.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for every 3 months for 1 year,&#xD;
      every 4 months for 1 year, and then periodically for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 29, 2014</start_date>
  <completion_date type="Anticipated">July 29, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 29, 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>PFS</measure>
    <time_frame>Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 3 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD of adding lenalidomide to the DA-EPOCH-R regimen as a front-line therapy in patients with DHL lymphomas (using CTCAE v 4.0) (Phase I)</measure>
    <time_frame>Up to 21 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PFS (Phase II)</measure>
    <time_frame>Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed at 1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PFS (Phase II)</measure>
    <time_frame>Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed at 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Add lenalidomide to the DA-EPOCH-R regimen as a front-line therapy in patients with DHL lymphomas (Phase I)</measure>
    <time_frame>Up to 18 weeks</time_frame>
    <description>Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 18 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate defined as the sum of partial response (PR) and complete response (CR) by computed tomography (CT) of positron emission tomography/CT and/or resolution of marrow-only involvement (if originally involved) (Phase I)</measure>
    <time_frame>Up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-tumor activity, calculated as the sum of stable disease, PR, and CR according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al (Phase I)</measure>
    <time_frame>Up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response, calculated as the duration from detecting any objective response until progression or death from any cause, according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al (Phase I)</measure>
    <time_frame>Time elapsed between initial documented PR or CR and first progression event, assessed up to 18 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events, defined as the occurrence of all grades of toxicity (using CTCAE version 4.0)</measure>
    <time_frame>Up to 21 days from last treatment</time_frame>
    <description>The occurrence and severity of each event will be recorded.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">46</enrollment>
  <condition>Adult Grade III Lymphomatoid Granulomatosis</condition>
  <condition>B-cell Chronic Lymphocytic Leukemia</condition>
  <condition>Contiguous Stage II Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma</condition>
  <condition>Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma</condition>
  <condition>Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma</condition>
  <condition>Contiguous Stage II Grade 1 Follicular Lymphoma</condition>
  <condition>Contiguous Stage II Grade 2 Follicular Lymphoma</condition>
  <condition>Contiguous Stage II Grade 3 Follicular Lymphoma</condition>
  <condition>Contiguous Stage II Mantle Cell Lymphoma</condition>
  <condition>Contiguous Stage II Marginal Zone Lymphoma</condition>
  <condition>Contiguous Stage II Small Lymphocytic Lymphoma</condition>
  <condition>Cutaneous B-cell Non-Hodgkin Lymphoma</condition>
  <condition>Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue</condition>
  <condition>Intraocular Lymphoma</condition>
  <condition>Nodal Marginal Zone B-cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Grade 1 Follicular Lymphoma</condition>
  <condition>Noncontiguous Stage II Grade 2 Follicular Lymphoma</condition>
  <condition>Noncontiguous Stage II Grade 3 Follicular Lymphoma</condition>
  <condition>Noncontiguous Stage II Mantle Cell Lymphoma</condition>
  <condition>Noncontiguous Stage II Marginal Zone Lymphoma</condition>
  <condition>Noncontiguous Stage II Small Lymphocytic Lymphoma</condition>
  <condition>Progressive Hairy Cell Leukemia, Initial Treatment</condition>
  <condition>Small Intestine Lymphoma</condition>
  <condition>Splenic Marginal Zone Lymphoma</condition>
  <condition>Stage 0 Chronic Lymphocytic Leukemia</condition>
  <condition>Stage I Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Stage I Adult Diffuse Mixed Cell Lymphoma</condition>
  <condition>Stage I Adult Diffuse Small Cleaved Cell Lymphoma</condition>
  <condition>Stage I Adult Hodgkin Lymphoma</condition>
  <condition>Stage I Adult Immunoblastic Large Cell Lymphoma</condition>
  <condition>Stage I Chronic Lymphocytic Leukemia</condition>
  <condition>Stage I Grade 1 Follicular Lymphoma</condition>
  <condition>Stage I Grade 2 Follicular Lymphoma</condition>
  <condition>Stage I Grade 3 Follicular Lymphoma</condition>
  <condition>Stage I Mantle Cell Lymphoma</condition>
  <condition>Stage I Marginal Zone Lymphoma</condition>
  <condition>Stage I Small Lymphocytic Lymphoma</condition>
  <condition>Stage II Adult Hodgkin Lymphoma</condition>
  <condition>Stage II Chronic Lymphocytic Leukemia</condition>
  <condition>Stage II Small Lymphocytic Lymphoma</condition>
  <condition>Stage III Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Stage III Adult Diffuse Mixed Cell Lymphoma</condition>
  <condition>Stage III Adult Diffuse Small Cleaved Cell Lymphoma</condition>
  <condition>Stage III Adult Hodgkin Lymphoma</condition>
  <condition>Stage III Adult Immunoblastic Large Cell Lymphoma</condition>
  <condition>Stage III Chronic Lymphocytic Leukemia</condition>
  <condition>Stage III Grade 1 Follicular Lymphoma</condition>
  <condition>Stage III Grade 2 Follicular Lymphoma</condition>
  <condition>Stage III Grade 3 Follicular Lymphoma</condition>
  <condition>Stage III Mantle Cell Lymphoma</condition>
  <condition>Stage III Marginal Zone Lymphoma</condition>
  <condition>Stage III Small Lymphocytic Lymphoma</condition>
  <condition>Stage IV Adult Diffuse Large Cell Lymphoma</condition>
  <condition>Stage IV Adult Diffuse Mixed Cell Lymphoma</condition>
  <condition>Stage IV Adult Diffuse Small Cleaved Cell Lymphoma</condition>
  <condition>Stage IV Adult Hodgkin Lymphoma</condition>
  <condition>Stage IV Adult Immunoblastic Large Cell Lymphoma</condition>
  <condition>Stage IV Chronic Lymphocytic Leukemia</condition>
  <condition>Stage IV Grade 1 Follicular Lymphoma</condition>
  <condition>Stage IV Grade 2 Follicular Lymphoma</condition>
  <condition>Stage IV Grade 3 Follicular Lymphoma</condition>
  <condition>Stage IV Mantle Cell Lymphoma</condition>
  <condition>Stage IV Marginal Zone Lymphoma</condition>
  <condition>Stage IV Small Lymphocytic Lymphoma</condition>
  <condition>Testicular Lymphoma</condition>
  <condition>Untreated Hairy Cell Leukemia</condition>
  <condition>Waldenström Macroglobulinemia</condition>
  <arm_group>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>INDUCTION PHASE: Patients receive lenalidomide PO daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
DA-EPOCH-R: Patients receive etoposide IV continuously on days 1-4, prednisone PO BID on days 1-5, vincristine sulfate IV continuously on days 1-4, doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.&#xD;
CONSOLIDATION PHASE: Patients who are transplantation (HSCT)-eligible receive BEAM-conditioning regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating physician. Patients who do not undergo HSCT in first remission receive lenalidomide maintenance for 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lenalidomide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>CC-5013</other_name>
    <other_name>IMiD-1</other_name>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>etoposide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>EPEG</other_name>
    <other_name>VP-16</other_name>
    <other_name>VP-16-213</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prednisone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>DeCortin</other_name>
    <other_name>Deltra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vincristine sulfate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>leurocristine sulfate</other_name>
    <other_name>VCR</other_name>
    <other_name>Vincasar PFS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>doxorubicin hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>ADM</other_name>
    <other_name>ADR</other_name>
    <other_name>Adria</other_name>
    <other_name>Adriamycin PFS</other_name>
    <other_name>Adriamycin RDF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>CPM</other_name>
    <other_name>CTX</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Endoxan</other_name>
    <other_name>Endoxana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 monoclonal antibody</other_name>
    <other_name>Mabthera</other_name>
    <other_name>MOAB IDEC-C2B8</other_name>
    <other_name>Rituxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>quality-of-life assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
    <other_name>quality of life assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (lenalidomide, DA-EPOCH-R)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. B-cell lymphoma with comprehensive immunohistochemistry (IHC) panel establishing&#xD;
             lineage (CD20, CD3) and cell of origin (CD10, BCL6 and MUM1) in addition to&#xD;
             proliferative/prognostic markers (Ki-67, C-myc and BCL2). DHL will be identified using&#xD;
             cytogenetics and/or immunohistochemistry as detailed in section 4.1.2 below.&#xD;
&#xD;
          2. To define DHL, patients must have evidence of C-myc [defined as: Cytogenetic evidence&#xD;
             (FISH or karyotype) of C-myc breaks (Increased copy number in itself is not considered&#xD;
             positivity for C-myc) OR Positive IHC defined as &gt;40% of the lymphoma cells staining&#xD;
             for C-myc] PLUS either:&#xD;
&#xD;
               1. Breaks in BCL-2 via cytogenetic studies or&#xD;
&#xD;
               2. BCL-2 immunopositivity in &gt;70% of lymphoma cells.&#xD;
&#xD;
          3. Patients are allowed to have received radiotherapy before enrollment if radiation was&#xD;
             given to alleviate pain and/or neurologic compromise as long as there remains areas of&#xD;
             measurable disease present. Further, at the investigator's discretion and for patients&#xD;
             who are unstable, one cycle of R-CHOP is allowed prior to enrollment but no more than&#xD;
             one cycle. For purposes of this trial, prednisone or other corticosteroids used for&#xD;
             non-lymphomatous conditions will be allowed. In addition, a prior/recent short course&#xD;
             (&lt; 2 weeks) of steroids for symptom relief of lymphoma-related symptoms will be&#xD;
             allowed.&#xD;
&#xD;
          4. AST and ALT &lt; 3 x upper limit of normal (ULN), and total bilirubin &lt;1.5 x ULN (with&#xD;
             exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver&#xD;
             involvement with NHL or stable chronic liver disease per investigator assessment).&#xD;
&#xD;
          5. Patients must have adequate renal function by virtue of GFR &gt; 50 ml/minute using&#xD;
             Cockroft-Gault formula.&#xD;
&#xD;
          6. Patients must have adequate bone marrow function (platelets &gt;100,000 and ANC &gt;1,200).&#xD;
             Patients with bone marrow involvement are allowed at the investigator's discretion&#xD;
             regardless of cytopenias.&#xD;
&#xD;
          7. ECOG PS 0-2.&#xD;
&#xD;
          8. Age ≥ 18 years.&#xD;
&#xD;
          9. All study participants must be registered into the mandatory lenalidomide REMS®&#xD;
             program, and be willing and able to comply with the requirements of the REMS® program.&#xD;
&#xD;
         10. Females of reproductive potential must adhere to the scheduled pregnancy testing as&#xD;
             required in the lenalidomide REMS® program. (Please see study schema for further&#xD;
             details)&#xD;
&#xD;
         11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients&#xD;
             intolerant to ASA may use warfarin or low molecular weight heparin).&#xD;
&#xD;
         12. Ability to read, understand, and sign a written informed consent approved by each&#xD;
             institutional IRB. Alternatively, patients with legal guardians who can read,&#xD;
             understand, and sign written informed consent may also enroll.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Prior therapy for lymphoma&#xD;
&#xD;
          2. Known CNS involvement&#xD;
&#xD;
          3. Known HIV positive status&#xD;
&#xD;
          4. Pregnant females&#xD;
&#xD;
          5. Burkitt and/or precursor lymphoblastic leukemia/lymphoma.&#xD;
&#xD;
          6. Prior pomalidomide exposure&#xD;
&#xD;
          7. Known hypersensitivity to lenalidomide or thalidomide&#xD;
&#xD;
          8. The development of erythema nodosum if characterized by a desquamating rash while&#xD;
             taking thalidomide or similar drugs.&#xD;
&#xD;
          9. Subjects who have currently active hepatic or biliary disease (with exception of&#xD;
             patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL&#xD;
             or stable chronic liver disease per investigator assessment).&#xD;
&#xD;
         10. Treatment with any known non-marketed drug substance or experimental therapy within 4&#xD;
             weeks prior to enrollment, or currently participating in any other interventional&#xD;
             clinical study for NHL or any other illness (except observational, prevention, and/or&#xD;
             registry trials).&#xD;
&#xD;
         11. No current malignancy. Subjects who have been free of malignancy for at least 2 years,&#xD;
             or have a history of completely resected non-melanoma skin cancer, or successfully&#xD;
             treated in situ carcinoma (any site) are eligible. Women with a history of cervical&#xD;
             cancers are allowed.&#xD;
&#xD;
         12. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or&#xD;
             antiviral treatment such as, but not limited to, chronic renal infection, chronic&#xD;
             chest infection with bronchiectasis, tuberculosis and active Hepatitis C.&#xD;
&#xD;
         13. History of significant cerebrovascular disease in the past 3 months or ongoing event&#xD;
             with active symptoms or sequelae.&#xD;
&#xD;
         14. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In&#xD;
             addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB&#xD;
             DNA test will be performed and if positive, the subject will be excluded if unable to&#xD;
             tolerate and/or receive anti-Hepatitis-B therapy. Positive serology because of prior&#xD;
             vaccination is allowed.&#xD;
&#xD;
         15. Positive serology for hepatitis C (HC) defined as a positive test for HCAb.&#xD;
&#xD;
         16. Inability to comply with study or follow-up testing and procedures.&#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>Sonali Smith</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Chicago</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital Cancer Care Institute</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NorthShore University HealthSystem</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <last_update_submitted>April 26, 2023</last_update_submitted>
  <last_update_submitted_qc>April 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2023</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>Leukemia</mesh_term>
    <mesh_term>Lymphoma, Follicular</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
    <mesh_term>Lymphoma, Mantle-Cell</mesh_term>
    <mesh_term>Lymphoma, B-Cell, Marginal Zone</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
    <mesh_term>Lymphoma, Large-Cell, Immunoblastic</mesh_term>
    <mesh_term>Plasmablastic Lymphoma</mesh_term>
    <mesh_term>Waldenstrom Macroglobulinemia</mesh_term>
    <mesh_term>Leukemia, Hairy Cell</mesh_term>
    <mesh_term>Lymphomatoid Granulomatosis</mesh_term>
    <mesh_term>Intraocular Lymphoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Etoposide phosphate</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/NCT02213913
org study id: 13-1406
secondary id: NCI-2014-01581
secondary id: IRB13-1406
secondary id: 13-1406
secondary id: P30CA014599
nct id: NCT02213913
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I/II trial studies the side effects and best dose of lenalidomide when given
      together with combination chemotherapy and to see how well they work in treating patients
      with v-myc myelocytomatosis viral oncogene homolog (avian) (MYC)-associated B-cell lymphomas.
      Lenalidomide may stop the growth of B-cell lymphomas by blocking the growth of new blood
      vessels necessary for cancer growth and by blocking some of the enzymes needed for cell
      growth. Biological therapies, such as lenalidomide, use substances made from living organisms
      that may stimulate or suppress the immune system in different ways and stop cancer cells from
      growing. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate,
      doxorubicin hydrochloride, cyclophosphamide, work in different ways to stop the growth of
      cancer cells, either by killing the cells, by stopping them from dividing, or by stopping
      them from spreading. Monoclonal antibodies, such as rituximab, may block cancer growth in
      different ways by targeting certain cells. Giving lenalidomide together with combination
      chemotherapy may be an effective treatment in patients with B-cell lymphoma.
PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of lenalidomide when added to dose-adjusted
      (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide,
      rituximab (EPOCH-R) (hereby termed "DA-EPOCH-RR") in patients with double hit lymphoma (DHL)
      lymphomas. (Phase I) II. To determine the 1- and 2-year progression free survival (PFS) of
      DA-EPOCH-RR in patients with DHL lymphomas. (Phase II)

      SECONDARY OBJECTIVES:

      I. Overall response rate, complete response, and duration of response. II. Quality of life
      (QOL) measures using standardized scales. III. Toxicity assessment using version 4.0 of the
      National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE)
      criteria.

      IV. Overall survival (OS) at 1 and 2 years.

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

      INDUCTION PHASE: Patients receive lenalidomide orally (PO) daily on days 1-14. Treatment
      repeats every 21 days for 6 courses in the absence of disease progression or unacceptable
      toxicity.

      DA-EPOCH-R: Patients receive etoposide intravenously (IV) continuously on days 1-4,
      prednisone PO twice daily (BID) on days 1-5, vincristine sulfate IV continuously on days 1-4,
      doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on
      day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment
      repeats every 21 days for 6 courses in the absence of disease progression or unacceptable
      toxicity.

      CONSOLIDATION PHASE: Patients who are transplantation (hematopoietic stem cell transplant
      [HSCT])-eligible receive BCNU, etoposide, cytarabine, and melphalan (BEAM)-conditioning
      regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating
      physician. Patients who do not undergo HSCT in first remission receive lenalidomide
      maintenance for 12 months.

      After completion of study treatment, patients are followed up for every 3 months for 1 year,
      every 4 months for 1 year, and then periodically for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS
time frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 3 years
measure: MTD of adding lenalidomide to the DA-EPOCH-R regimen as a front-line therapy in patients with DHL lymphomas (using CTCAE v 4.0) (Phase I)
time frame: Up to 21 days
measure: PFS (Phase II)
time frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed at 1 year
measure: PFS (Phase II)
time frame: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed at 2 years
measure: Add lenalidomide to the DA-EPOCH-R regimen as a front-line therapy in patients with DHL lymphomas (Phase I)
time frame: Up to 18 weeks
description: Time elapsed between treatment initiation and tumor progression or death from any cause (whichever occurs first), assessed up to 18 weeks
measure: Overall response rate defined as the sum of partial response (PR) and complete response (CR) by computed tomography (CT) of positron emission tomography/CT and/or resolution of marrow-only involvement (if originally involved) (Phase I)
time frame: Up to 18 weeks
measure: Anti-tumor activity, calculated as the sum of stable disease, PR, and CR according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al (Phase I)
time frame: Up to 18 weeks
measure: Duration of response, calculated as the duration from detecting any objective response until progression or death from any cause, according to the Revised Response Criteria for Malignant Lymphoma and Cheson et al (Phase I)
time frame: Time elapsed between initial documented PR or CR and first progression event, assessed up to 18 weeks
measure: Incidence of adverse events, defined as the occurrence of all grades of toxicity (using CTCAE version 4.0)
time frame: Up to 21 days from last treatment
description: The occurrence and severity of each event will be recorded.
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
arm group type: Experimental
description: INDUCTION PHASE: Patients receive lenalidomide PO daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
DA-EPOCH-R: Patients receive etoposide IV continuously on days 1-4, prednisone PO BID on days 1-5, vincristine sulfate IV continuously on days 1-4, doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION PHASE: Patients who are transplantation (HSCT)-eligible receive BEAM-conditioning regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating physician. Patients who do not undergo HSCT in first remission receive lenalidomide maintenance for 12 months.
intervention type: Drug
intervention name: lenalidomide
description: Given PO
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: CC-5013
other name: IMiD-1
other name: Revlimid
intervention type: Drug
intervention name: etoposide
description: Given IV
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: EPEG
other name: VP-16
other name: VP-16-213
intervention type: Drug
intervention name: prednisone
description: Given PO
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: DeCortin
other name: Deltra
intervention type: Drug
intervention name: vincristine sulfate
description: Given IV
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: leurocristine sulfate
other name: VCR
other name: Vincasar PFS
intervention type: Drug
intervention name: doxorubicin hydrochloride
description: Given IV
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: ADM
other name: ADR
other name: Adria
other name: Adriamycin PFS
other name: Adriamycin RDF
intervention type: Drug
intervention name: cyclophosphamide
description: Given IV
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: CPM
other name: CTX
other name: Cytoxan
other name: Endoxan
other name: Endoxana
intervention type: Biological
intervention name: rituximab
description: Given IV
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: IDEC-C2B8
other name: IDEC-C2B8 monoclonal antibody
other name: Mabthera
other name: MOAB IDEC-C2B8
other name: Rituxan
intervention type: Other
intervention name: quality-of-life assessment
description: Ancillary studies
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
other name: quality of life assessment
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (lenalidomide, DA-EPOCH-R)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sonali Smith
role: Principal Investigator
affiliation: University of Chicago
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Lymphoma, Follicular
mesh term: Lymphoma, Non-Hodgkin
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Hodgkin Disease
mesh term: Lymphoma, Mantle-Cell
mesh term: Lymphoma, B-Cell, Marginal Zone
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Lymphoma, Large-Cell, Immunoblastic
mesh term: Plasmablastic Lymphoma
mesh term: Waldenstrom Macroglobulinemia
mesh term: Leukemia, Hairy Cell
mesh term: Lymphomatoid Granulomatosis
mesh term: Intraocular Lymphoma
mesh term: Prednisone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Etoposide
mesh term: Vincristine
mesh term: Lenalidomide
mesh term: Etoposide phosphate