<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/NCT02254239</url>
  </required_header>
  <id_info>
    <org_study_id>MC1387</org_study_id>
    <secondary_id>NCI-2014-01804</secondary_id>
    <secondary_id>MC1387</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT02254239</nct_id>
  </id_info>
  <brief_title>Everolimus and Brentuximab Vedotin in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma</brief_title>
  <official_title>Phase 1 Study of Everolimus in Combination With Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and the best dose of everolimus when given&#xD;
      together with brentuximab vedotin in treating patients with Hodgkin lymphoma that has come&#xD;
      back (relapsed) or is not responding to treatment (refractory). Everolimus may stop the&#xD;
      growth of cancer cells by blocking some of the enzymes needed for cell growth. Brentuximab&#xD;
      vedotin may interfere with the ability of cancer cells to grow and spread by binding to a&#xD;
      protein on the surface of cancer cells and then releasing a cancer-killing substance to them.&#xD;
      Giving everolimus together with brentuximab vedotin may be a better treatment for Hodgkin&#xD;
      lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the safety and optimal dose of everolimus given in combination with&#xD;
      brentuximab vedotin in relapsed or refractory Hodgkin lymphoma patients.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the efficacy of everolimus in combination with brentuximab vedotin in&#xD;
      relapsed or refractory Hodgkin lymphoma.&#xD;
&#xD;
      II. To evaluate duration of response, progression free survival, and overall survival.&#xD;
&#xD;
      III. To evaluate response by positron emission tomography (PET)-computed tomography (CT)&#xD;
      based response criteria.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To assess cytokines and free light chain before and after therapy.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of everolimus.&#xD;
&#xD;
      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and&#xD;
      everolimus orally (PO) once daily (QD) or every other day (QOD) on days 1-21. Treatment&#xD;
      repeats every 21 days for up to 15 courses in the absence of disease progression or&#xD;
      unacceptable toxicity. Patients then receive brentuximab vedotin IV over 30 minutes on day 1&#xD;
      and everolimus PO QD or every other day on days 1-84 for 1 course.&#xD;
&#xD;
      MAINTENANCE THERAPY: Beginning on course 17, patients receive everolimus PO QD, QOD, twice&#xD;
      weekly, or thrice weekly on days 1-84. Courses repeat every 84 days in the absence of disease&#xD;
      progression and unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 6 months for 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    funding withdrawal&#xD;
  </why_stopped>
  <start_date type="Actual">February 4, 2016</start_date>
  <completion_date type="Actual">December 12, 2018</completion_date>
  <primary_completion_date type="Actual">December 12, 2018</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>Maximum tolerated dose (MTD) of everolimus in combination with brentuximab vedotin, graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>21 days</time_frame>
    <description>MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete response (CR) rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>The CR rate will be estimated by the number of patients with an objective status of CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>From date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 1 year</time_frame>
    <description>If an adequate number of events are seen, the distribution of duration of response will be estimated using the method of Kaplan-Meier. Otherwise, duration of response will be summarized descriptively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR) (complete response [CR] or partial response [PR])</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>The ORR will be estimated by the number of patients with an objective status of CR or PR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 1 year</time_frame>
    <description>The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response evaluated according to positron emission tomography/computed tomography-based response criteria</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>The number of patients who achieve a complete metabolic response or partial metabolic response will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time</measure>
    <time_frame>Time from registration to death due to any cause, assessed up to 1 year</time_frame>
    <description>The distribution of survival time will be estimated using the method of Kaplan-Meier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment evaluated via Common Terminology Criteria for Adverse Events (CTCAE) version 4.0</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in cytokines</measure>
    <time_frame>Baseline to up to day 1 of course 2</time_frame>
    <description>Changes in these values will be both graphically and quantitatively summarized and explored. Paired sample approaches (Wilcoxon signed rank test) for these types of quantitative measures will be used to assess differences over time. In addition, these values will be explored in relation to clinical outcomes such as response (responder vs non-responder as well as by quality of response, i.e. CR versus PR).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in serum immunoglobulin free light chain</measure>
    <time_frame>Baseline to up to day 1 of course 2</time_frame>
    <description>Changes in these values will be both graphically and quantitatively summarized and explored. Paired sample approaches (Wilcoxon signed rank test) for these types of quantitative measures will be used to assess differences over time. In addition, these values will be explored in relation to clinical outcomes such as response (responder vs non-responder as well as by quality of response, i.e. CR versus PR).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Recurrent Hodgkin Lymphoma</condition>
  <condition>Refractory Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (everolimus, brentuximab vedotin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or QOD on days 1-21. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity. Patients then receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or every other day on days 1-84 for 1 course.&#xD;
MAINTENANCE THERAPY: Beginning on course 17, patients receive everolimus PO QD, QOD, twice weekly, or thrice weekly on days 1-84. Courses repeat every 84 days in the absence of disease progression and unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (everolimus, brentuximab vedotin)</arm_group_label>
    <other_name>ADC SGN-35</other_name>
    <other_name>Adcetris</other_name>
    <other_name>Anti-CD30 Antibody-Drug Conjugate SGN-35</other_name>
    <other_name>Anti-CD30 Monoclonal Antibody-MMAE SGN-35</other_name>
    <other_name>Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35</other_name>
    <other_name>cAC10-vcMMAE</other_name>
    <other_name>SGN-35</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Everolimus</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (everolimus, brentuximab vedotin)</arm_group_label>
    <other_name>42-O-(2-Hydroxy)ethyl Rapamycin</other_name>
    <other_name>Afinitor</other_name>
    <other_name>Certican</other_name>
    <other_name>RAD 001</other_name>
    <other_name>RAD001</other_name>
    <other_name>Votubia</other_name>
    <other_name>Zortress</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (everolimus, brentuximab vedotin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (everolimus, brentuximab vedotin)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy-proven relapsed (response to last treatment &gt; 6 months duration), refractory&#xD;
             (no response to last treatment or response duration &lt; 6 months) or residual Hodgkin&#xD;
             lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy &lt;&#xD;
             180 days prior to registration on this protocol with no intervening therapy and tissue&#xD;
             is available for translational research studies&#xD;
&#xD;
          -  Eligible to receive standard brentuximab vedotin for relapsed Hodgkin lymphoma&#xD;
&#xD;
          -  Measurable disease by CT or magnetic resonance imaging (MRI) or the CT portion of the&#xD;
             PET/CT: must have at least one lesion that has a single diameter of &gt;= 2 cm&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1000/uL&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt;= 9 g/dl&#xD;
&#xD;
          -  Platelet (PLT) &gt;= 75,000/uL&#xD;
&#xD;
          -  Serum total bilirubin within normal range (or =&lt; 1.5 x upper limit of normal [ULN] if&#xD;
             liver metastases are present; or total bilirubin =&lt; 3.0 x ULN with direct bilirubin&#xD;
             within normal range in patients with well documented Gilbert syndrome)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Negative serum pregnancy test done =&lt; 7 days prior to registration, for women of&#xD;
             childbearing potential only&#xD;
&#xD;
          -  Provide informed written consent&#xD;
&#xD;
          -  Willing to return to Mayo Clinic for follow-up&#xD;
&#xD;
          -  Willing to provide blood and tissue samples for correlative research purposes&#xD;
&#xD;
          -  Willingness to take everolimus orally and maintain a pill diary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any of the following&#xD;
&#xD;
               -  Pregnant women&#xD;
&#xD;
               -  Nursing women&#xD;
&#xD;
               -  Women of childbearing potential who are unwilling to employ highly effective&#xD;
                  contraception while on study treatment and for 6 months after the final dose of&#xD;
                  treatment; NOTE: women of childbearing potential are defined as all women&#xD;
                  physiologically capable of becoming pregnant&#xD;
&#xD;
               -  Men of childbearing potential who are unwilling to employ highly effective&#xD;
                  contraception while on study treatment and for 6 months after the final dose of&#xD;
                  treatment and should not father a child during this time; NOTE: men of&#xD;
                  childbearing potential are defined as all males physiologically capable of&#xD;
                  conceiving offspring&#xD;
&#xD;
          -  Candidate for known standard therapy for the patient's disease that is potentially&#xD;
             curative&#xD;
&#xD;
          -  Therapy with myelosuppressive chemotherapy or biologic therapy &lt; 21 days prior to&#xD;
             registration unless the patient has recovered from the nadir of the previous treatment&#xD;
             to a level that meets the inclusion eligibility criteria of this protocol&#xD;
&#xD;
          -  Patients who have received any continuous or intermittent small molecule therapeutics&#xD;
             (excluding monoclonal antibodies) =&lt; 5 effective half-lives prior to registration or&#xD;
             who have not recovered from side effects of such therapy&#xD;
&#xD;
          -  Received wide field radiotherapy =&lt; 28 days or limited field radiation for palliation&#xD;
             =&lt; 14 days prior to registration or who have not recovered from side effects of such&#xD;
             therapy&#xD;
&#xD;
          -  Receiving corticosteroids &gt; 20 mg of prednisone per day (or equivalent); Note: the&#xD;
             dose should be noted on the medication record each cycle&#xD;
&#xD;
          -  Persistent toxicities &gt;= grade 2 from prior chemotherapy or biological therapy&#xD;
             regardless of interval since last treatment&#xD;
&#xD;
          -  Patients who have any severe and/or uncontrolled medical conditions or other&#xD;
             conditions that could affect their participation in the study such as:&#xD;
&#xD;
               -  Symptomatic congestive heart failure of New York Heart Association class III or&#xD;
                  IV&#xD;
&#xD;
               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial&#xD;
                  infarction within 6 months prior to registration, serious uncontrolled cardiac&#xD;
                  arrhythmia or any other clinically significant cardiac disease&#xD;
&#xD;
               -  Severely impaired lung function as defined as spirometry and diffusion capacity&#xD;
                  of carbon monoxide (DLCO) that is less than 50% of the normal predicted value&#xD;
                  and/or oxygen (O2) saturation that is 88% or less at rest on room air&#xD;
&#xD;
               -  Uncontrolled diabetes as defined by fasting serum glucose &gt; 1.5 x ULN (Note:&#xD;
                  optimal glycemic control should be achieved before starting everolimus)&#xD;
&#xD;
               -  Active (acute or chronic) or uncontrolled severe infections&#xD;
&#xD;
          -  Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy&#xD;
             considered investigational (utilized for a non-Food and Drug Administration&#xD;
             [FDA]-approved indication and in the context of a research investigation)&#xD;
&#xD;
          -  Known positivity for human immunodeficiency virus (HIV); Note: baseline testing for&#xD;
             HIV is not required&#xD;
&#xD;
          -  Active hepatitis B or C with uncontrolled disease&#xD;
&#xD;
               -  Note: a detailed assessment of hepatitis B/C medical history and risk factors&#xD;
                  must be done at screening for all patients; hepatitis B virus surface antigen&#xD;
                  (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain&#xD;
                  reaction (PCR) testing are required at screening for all patients with a positive&#xD;
                  medical history based on risk factors and/or confirmation of prior hepatitis B&#xD;
                  virus (HBV) infection&#xD;
&#xD;
          -  Other active malignancy requiring treatment that would interfere with the assessments&#xD;
             of response of the lymphoma to protocol treatment&#xD;
&#xD;
          -  Inability to swallow or impairment of gastrointestinal function or gastrointestinal&#xD;
             disease that may significantly alter the absorption of the drugs (e.g., ulcerative&#xD;
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small&#xD;
             bowel resection) that would preclude use of oral medications&#xD;
&#xD;
          -  Major surgery =&lt; 14 days prior to registration or have not recovered from side effects&#xD;
             of such therapy&#xD;
&#xD;
          -  Treated with any hematopoietic colony-stimulating growth factors (e.g.,&#xD;
             granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage&#xD;
             colony-stimulating factor [GM-CSF]) =&lt; 2 weeks prior to study registration; NOTE:&#xD;
             erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study&#xD;
             registration, may be continued&#xD;
&#xD;
          -  Pre-existing neuropathy of &gt;= grade 2&#xD;
&#xD;
          -  Patients receiving strong inhibitors of cytochrome P450 family 3, subfamily A,&#xD;
             polypeptide 4 (CYP3A4)&#xD;
&#xD;
               -  Use of the following strong or moderate inhibitors are prohibited =&lt; 7 days prior&#xD;
                  to registration&#xD;
&#xD;
                    -  Boceprevir (Victrelis [TM])&#xD;
&#xD;
                    -  Clarithromycin (Biaxin, Biaxin XL)&#xD;
&#xD;
                    -  Conivaptan (Vaprisol)&#xD;
&#xD;
                    -  Itraconazole (Sporanox)&#xD;
&#xD;
                    -  Ketoconazole (Nizoral)&#xD;
&#xD;
                    -  Nefazodone (Serzone)&#xD;
&#xD;
                    -  Posaconazole (Noxafil)&#xD;
&#xD;
                    -  Telithromycin (Ketek)&#xD;
&#xD;
                    -  Voriconazole (Vfend)&#xD;
&#xD;
               -  Use of the following inducers are prohibited =&lt; 12 days prior to registration&#xD;
&#xD;
                    -  Bosentan (Tracleer)&#xD;
&#xD;
                    -  Carbamazepine (Carbatrol, Epitol, Equetro [TM], Tegretol, Tegretol-XR)&#xD;
&#xD;
                    -  Modafinil (Provigil)&#xD;
&#xD;
                    -  Phenobarbital (Luminal)&#xD;
&#xD;
                    -  Phenytoin (Dilantin, Phenytek)&#xD;
&#xD;
                    -  Rifabutin (Mycobutin)&#xD;
&#xD;
                    -  Rifampin (Rifadin)&#xD;
&#xD;
                    -  St. John's wort&#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>Patrick Johnston</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2014</study_first_posted>
  <last_update_submitted>December 10, 2019</last_update_submitted>
  <last_update_submitted_qc>December 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2019</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>Hodgkin Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Brentuximab Vedotin</mesh_term>
    <mesh_term>Everolimus</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoconjugates</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/NCT02254239
org study id: MC1387
secondary id: NCI-2014-01804
secondary id: MC1387
secondary id: P30CA015083
nct id: NCT02254239
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I trial studies the side effects and the best dose of everolimus when given
      together with brentuximab vedotin in treating patients with Hodgkin lymphoma that has come
      back (relapsed) or is not responding to treatment (refractory). Everolimus may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth. Brentuximab
      vedotin may interfere with the ability of cancer cells to grow and spread by binding to a
      protein on the surface of cancer cells and then releasing a cancer-killing substance to them.
      Giving everolimus together with brentuximab vedotin may be a better treatment for Hodgkin
      lymphoma.
PRIMARY OBJECTIVES:

      I. To determine the safety and optimal dose of everolimus given in combination with
      brentuximab vedotin in relapsed or refractory Hodgkin lymphoma patients.

      SECONDARY OBJECTIVES:

      I. To determine the efficacy of everolimus in combination with brentuximab vedotin in
      relapsed or refractory Hodgkin lymphoma.

      II. To evaluate duration of response, progression free survival, and overall survival.

      III. To evaluate response by positron emission tomography (PET)-computed tomography (CT)
      based response criteria.

      TERTIARY OBJECTIVES:

      I. To assess cytokines and free light chain before and after therapy.

      OUTLINE: This is a dose-escalation study of everolimus.

      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and
      everolimus orally (PO) once daily (QD) or every other day (QOD) on days 1-21. Treatment
      repeats every 21 days for up to 15 courses in the absence of disease progression or
      unacceptable toxicity. Patients then receive brentuximab vedotin IV over 30 minutes on day 1
      and everolimus PO QD or every other day on days 1-84 for 1 course.

      MAINTENANCE THERAPY: Beginning on course 17, patients receive everolimus PO QD, QOD, twice
      weekly, or thrice weekly on days 1-84. Courses repeat every 84 days in the absence of disease
      progression and unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) of everolimus in combination with brentuximab vedotin, graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: 21 days
description: MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
measure: Complete response (CR) rate
time frame: Up to 1 year
description: The CR rate will be estimated by the number of patients with an objective status of CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.
measure: Duration of response
time frame: From date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 1 year
description: If an adequate number of events are seen, the distribution of duration of response will be estimated using the method of Kaplan-Meier. Otherwise, duration of response will be summarized descriptively.
measure: Overall response rate (ORR) (complete response [CR] or partial response [PR])
time frame: Up to 1 year
description: The ORR will be estimated by the number of patients with an objective status of CR or PR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
measure: Progression-free survival
time frame: Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 1 year
description: The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
measure: Response evaluated according to positron emission tomography/computed tomography-based response criteria
time frame: Up to 1 year
description: The number of patients who achieve a complete metabolic response or partial metabolic response will be assessed.
measure: Survival time
time frame: Time from registration to death due to any cause, assessed up to 1 year
description: The distribution of survival time will be estimated using the method of Kaplan-Meier.
measure: Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment evaluated via Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
time frame: Up to 1 year
description: Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized.
measure: Change in cytokines
time frame: Baseline to up to day 1 of course 2
description: Changes in these values will be both graphically and quantitatively summarized and explored. Paired sample approaches (Wilcoxon signed rank test) for these types of quantitative measures will be used to assess differences over time. In addition, these values will be explored in relation to clinical outcomes such as response (responder vs non-responder as well as by quality of response, i.e. CR versus PR).
measure: Change in serum immunoglobulin free light chain
time frame: Baseline to up to day 1 of course 2
description: Changes in these values will be both graphically and quantitatively summarized and explored. Paired sample approaches (Wilcoxon signed rank test) for these types of quantitative measures will be used to assess differences over time. In addition, these values will be explored in relation to clinical outcomes such as response (responder vs non-responder as well as by quality of response, i.e. CR versus PR).
arm group label: Treatment (everolimus, brentuximab vedotin)
arm group type: Experimental
description: Patients receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or QOD on days 1-21. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity. Patients then receive brentuximab vedotin IV over 30 minutes on day 1 and everolimus PO QD or every other day on days 1-84 for 1 course.
MAINTENANCE THERAPY: Beginning on course 17, patients receive everolimus PO QD, QOD, twice weekly, or thrice weekly on days 1-84. Courses repeat every 84 days in the absence of disease progression and unacceptable toxicity.
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Given IV
arm group label: Treatment (everolimus, brentuximab vedotin)
other name: ADC SGN-35
other name: Adcetris
other name: Anti-CD30 Antibody-Drug Conjugate SGN-35
other name: Anti-CD30 Monoclonal Antibody-MMAE SGN-35
other name: Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35
other name: cAC10-vcMMAE
other name: SGN-35
intervention type: Drug
intervention name: Everolimus
description: Given PO
arm group label: Treatment (everolimus, brentuximab vedotin)
other name: 42-O-(2-Hydroxy)ethyl Rapamycin
other name: Afinitor
other name: Certican
other name: RAD 001
other name: RAD001
other name: Votubia
other name: Zortress
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (everolimus, brentuximab vedotin)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (everolimus, brentuximab vedotin)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick Johnston
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Antineoplastic Agents, Immunological
mesh term: Brentuximab Vedotin
mesh term: Everolimus
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoconjugates