<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/NCT02227199</url>
  </required_header>
  <id_info>
    <org_study_id>9111</org_study_id>
    <secondary_id>NCI-2014-01782</secondary_id>
    <secondary_id>9111</secondary_id>
    <secondary_id>P30CA015704</secondary_id>
    <secondary_id>RG1714038</secondary_id>
    <nct_id>NCT02227199</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma</brief_title>
  <acronym>BV-ICE</acronym>
  <official_title>A Phase I/II Trial of Brentuximab Vedotin (BV), Ifosfamide (I), Carboplatin (C), and Etoposide (E) for Patients With Relapsed or Refractory Hodgkin Lymphoma (BV-ICE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Washington</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 phase I/II trial studies the side effects and best dose of brentuximab vedotin that can&#xD;
      be combined with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin&#xD;
      lymphoma that has come back (relapsed) or is not responding to treatment (refractory).&#xD;
      Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in&#xD;
      different ways by targeting certain cells. Chemotherapy drugs, such as ifosfamide,&#xD;
      carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either&#xD;
      by killing the cells, by stopping them from dividing, or by stopping them from spreading.&#xD;
      Giving brentuximab vedotin together with an ifosfamide, carboplatin, and etoposide&#xD;
      chemotherapy regimen may kill more cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine maximally tolerated dose of brentuximab vedotin that can be combined with&#xD;
      ifosfamide, carboplatin and etoposide chemotherapy in patients with relapsed or refractory&#xD;
      Hodgkin lymphoma.&#xD;
&#xD;
      II. To gain a preliminary assessment of the efficacy of the above regimen.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the safety and toxicity of the above regimen.&#xD;
&#xD;
      II. To determine the ability to proceed to peripheral blood stem cell collection following&#xD;
      the above regimen (the impact of above regimen on stem cell reserve).&#xD;
&#xD;
      III. To assess the impact of this regimen on biomarkers from the microenvironment in Hodgkin&#xD;
      lymphoma tumors.&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase&#xD;
      II study.&#xD;
&#xD;
      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 8;&#xD;
      ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1&#xD;
      hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease&#xD;
      progression or unacceptable toxicity. Patients planning to go on to consolidative high-dose&#xD;
      therapy (HDT) and autologous stem cell transplantation (ASCT) may undergo peripheral blood&#xD;
      stem cell (PBSC) mobilization following the 2nd course of study therapy at the discretion of&#xD;
      the treating physician.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 1 year and&#xD;
      then every 6 months for 4 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 10, 2014</start_date>
  <completion_date type="Anticipated">September 30, 2025</completion_date>
  <primary_completion_date type="Actual">March 30, 2020</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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy</measure>
    <time_frame>Up to 28 days following the second course of chemotherapy, approximately 70 days</time_frame>
    <description>Will be defined as the dose at which =&lt; 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Patients That Achieve a Complete Remission Following Study Treatment</measure>
    <time_frame>3 weeks following the completion of chemotherapy</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>2 Year Overall Survival</measure>
    <time_frame>Up to 2 years from initiation of study therapy.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2 Year Progression-free Survival</measure>
    <time_frame>Up to 2 years from initiation of therapy.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Recurrent Hodgkin Lymphoma</condition>
  <condition>Refractory Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</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>Carboplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <other_name>Blastocarb</other_name>
    <other_name>Carboplat</other_name>
    <other_name>Carboplatin Hexal</other_name>
    <other_name>Carboplatino</other_name>
    <other_name>Carbosin</other_name>
    <other_name>Carbosol</other_name>
    <other_name>Carbotec</other_name>
    <other_name>CBDCA</other_name>
    <other_name>Displata</other_name>
    <other_name>Ercar</other_name>
    <other_name>JM-8</other_name>
    <other_name>Nealorin</other_name>
    <other_name>Novoplatinum</other_name>
    <other_name>Paraplatin</other_name>
    <other_name>Paraplatin AQ</other_name>
    <other_name>Paraplatine</other_name>
    <other_name>Platinwas</other_name>
    <other_name>Ribocarbo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <other_name>Demethyl Epipodophyllotoxin Ethylidine Glucoside</other_name>
    <other_name>EPEG</other_name>
    <other_name>Lastet</other_name>
    <other_name>Toposar</other_name>
    <other_name>Vepesid</other_name>
    <other_name>VP 16-213</other_name>
    <other_name>VP-16</other_name>
    <other_name>VP-16-213</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ifosfamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <other_name>Asta Z 4942</other_name>
    <other_name>Asta Z-4942</other_name>
    <other_name>Cyfos</other_name>
    <other_name>Holoxan</other_name>
    <other_name>Holoxane</other_name>
    <other_name>Ifex</other_name>
    <other_name>IFO</other_name>
    <other_name>IFO-Cell</other_name>
    <other_name>Ifolem</other_name>
    <other_name>Ifomida</other_name>
    <other_name>Ifomide</other_name>
    <other_name>Ifosfamidum</other_name>
    <other_name>Ifoxan</other_name>
    <other_name>IFX</other_name>
    <other_name>Iphosphamid</other_name>
    <other_name>Iphosphamide</other_name>
    <other_name>Iso-Endoxan</other_name>
    <other_name>Isoendoxan</other_name>
    <other_name>Isophosphamide</other_name>
    <other_name>Mitoxana</other_name>
    <other_name>MJF 9325</other_name>
    <other_name>MJF-9325</other_name>
    <other_name>Naxamide</other_name>
    <other_name>Seromida</other_name>
    <other_name>Tronoxal</other_name>
    <other_name>Z 4942</other_name>
    <other_name>Z-4942</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
    <arm_group_label>Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have primary refractory or first relapse of cluster of differentiation&#xD;
             30 (CD30)+ Hodgkin lymphoma&#xD;
&#xD;
          -  Patients must have measurable disease defined as lesions that can be accurately&#xD;
             measured in two dimensions by computed tomography (CT), magnetic resonance imaging&#xD;
             (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional&#xD;
             technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions&#xD;
             with both diameters &gt;= 2 cm; further, at least 1 of these lesions must be positive by&#xD;
             positron emission tomography (PET) scan (i.e., Deauville score of 4 or more); Note: CT&#xD;
             scans remain the standard for evaluation of nodal disease&#xD;
&#xD;
          -  Patients must have a CT of chest, abdomen, and pelvis with PET within 28 days of&#xD;
             enrollment; patients with evidence of lymphadenopathy in the neck must have a&#xD;
             dedicated CT of neck&#xD;
&#xD;
          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0 or 1 (performance status of 2 will be allowed if poor performance status is thought&#xD;
             to be directly secondary to patient's Hodgkin lymphoma [HL])&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500/uL, performed within 28 days prior to&#xD;
             registration&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL (without transfusion or growth factor support), performed&#xD;
             within 28 days prior to registration&#xD;
&#xD;
          -  Serum creatinine &lt; 1.5 mg/dl or creatinine clearance (CrCl) &gt; 60 mL/min, performed&#xD;
             within 28 days prior to registration&#xD;
&#xD;
          -  Total bilirubin &lt; 2 times upper limit of normal (unless due to Gilbert's syndrome),&#xD;
             performed within 28 days prior to registration&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) &lt; 2.5 times upper limit of normal, performed within&#xD;
             28 days prior to registration&#xD;
&#xD;
          -  All patients must be informed of the investigational nature of this study and have&#xD;
             given written consent in accordance with institutional and federal guidelines&#xD;
&#xD;
          -  Patients must be anticipated to complete 2 cycles of chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients known to be positive for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Pregnant or nursing women; men or women of reproductive potential may not participate&#xD;
             unless they have agreed to use an effective contraceptive method&#xD;
&#xD;
          -  Patients with other prior malignancies except for adequately treated basal cell&#xD;
             carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or&#xD;
             other cancer from which the patient has been disease-free for 5 years or greater,&#xD;
             unless approved by the protocol chair or co-chair&#xD;
&#xD;
          -  Patients with known allergy, intolerance, or resistance (i.e., remission duration less&#xD;
             than 6 months or lack of response) to ifosfamide, carboplatin, or etoposide&#xD;
&#xD;
          -  Patients with evidence of active central nervous system lymphoma&#xD;
&#xD;
          -  Patients with prior receipt of brentuximab vedotin&#xD;
&#xD;
          -  Patients with peripheral neuropathy of &gt; grade 1&#xD;
&#xD;
          -  Patients who have other medical conditions that would contraindicate treatment with&#xD;
             aggressive chemotherapy (including active infection, uncontrolled hypertension,&#xD;
             congestive heart failure, unstable angina pectoris, myocardial infarction within the&#xD;
             past 6 months, or uncontrolled arrhythmia); if the patient's cardiac history is&#xD;
             questionable, a measurement of left ventricular ejection fraction should be obtained&#xD;
             within 42 days prior to registration; patients with left ventricular ejection fraction&#xD;
             &lt; 50% are not eligible&#xD;
&#xD;
          -  Prior failed (&lt; 5 x 10^6 CD34/kg) peripheral blood stem cell (PBSC) collection&#xD;
&#xD;
          -  Patients who had pelvic radiation within 12 months&#xD;
&#xD;
          -  Previous chemotherapy/immunotherapy within 3 weeks before study entry&#xD;
&#xD;
          -  Concurrent use of other anti-cancer agents or experimental treatments&#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>Ajay Gopal</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fred Hutch/University of Washington Cancer Consortium</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <results_first_submitted>March 24, 2021</results_first_submitted>
  <results_first_submitted_qc>May 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2021</results_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Washington</investigator_affiliation>
    <investigator_full_name>Ajay Gopal</investigator_full_name>
    <investigator_title>Professor, Department of Medicine, Division of Oncology</investigator_title>
  </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>Carboplatin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Etoposide phosphate</mesh_term>
    <mesh_term>Ifosfamide</mesh_term>
    <mesh_term>Isophosphamide mustard</mesh_term>
    <mesh_term>Brentuximab Vedotin</mesh_term>
    <mesh_term>Podophyllotoxin</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 9, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/99/NCT02227199/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab Vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="P2">
          <title>Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="P3">
          <title>Phase 2: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="B2">
          <title>Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="B3">
          <title>Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="39"/>
            <count group_id="B4" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="39"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="27"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="32"/>
                    <measurement group_id="B4" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="39"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy</title>
        <description>Will be defined as the dose at which =&lt; 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.</description>
        <time_frame>Up to 28 days following the second course of chemotherapy, approximately 70 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Brentuximab, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy</title>
          <description>Will be defined as the dose at which =&lt; 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.</description>
          <units>mg/kg</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Patients That Achieve a Complete Remission Following Study Treatment</title>
        <time_frame>3 weeks following the completion of chemotherapy</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab Vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O3">
            <title>Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab Vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients That Achieve a Complete Remission Following Study Treatment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>2 Year Overall Survival</title>
        <time_frame>Up to 2 years from initiation of study therapy.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O3">
            <title>Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>2 Year Overall Survival</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>2 Year Progression-free Survival</title>
        <time_frame>Up to 2 years from initiation of therapy.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O2">
            <title>Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
          <group group_id="O3">
            <title>Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
            <description>Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
          </group>
        </group_list>
        <measure>
          <title>2 Year Progression-free Survival</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected starting after the first dose of study treatment and collected through 30 days after the last dose of study drug, or until the patient receives an alternative anti-cancer therapy, whichever date comes first, approximately 60 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab vedotin 1.2mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="E2">
          <title>Phase 1: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.&#xD;
Brentuximab Vedotin: Given IV&#xD;
Carboplatin: Given IV&#xD;
Etoposide: Given IV&#xD;
Ifosfamide: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies</description>
        </group>
        <group group_id="E3">
          <title>Phase 2: Dose Expansion, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)</title>
          <description>Patients receive brentuximab vedotin 1.5mg/kg IV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="11" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic Ketoacidosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neutropenic Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Septic Shock</sub_title>
                <counts group_id="E1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Elevated Lactate</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Sweet Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Erythematous Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pulmonary Embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="39" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="10" subjects_affected="8" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="11" subjects_affected="11" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="13" subjects_affected="11" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="19" subjects_affected="18" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="15" subjects_affected="10" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="23" subjects_affected="18" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="40" subjects_affected="29" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Gastroesophageal Reflux Disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="12" subjects_affected="12" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Mucositis Oral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="19" subjects_affected="16" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Night Sweats</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="8" subjects_affected="7" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain at Hickman Site</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="30" subjects_affected="12" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="17" subjects_affected="10" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="8" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="13" subjects_affected="12" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Bone Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="18" subjects_affected="15" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="12" subjects_affected="10" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Allergic Rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="19" subjects_affected="19" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" events="8" subjects_affected="7" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Ajay Gopal</name_or_title>
      <organization>University of Washington</organization>
      <phone>26-606-2037</phone>
      <email>agopal@uw.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02227199
org study id: 9111
secondary id: NCI-2014-01782
secondary id: 9111
secondary id: P30CA015704
secondary id: RG1714038
nct id: NCT02227199
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I/II trial studies the side effects and best dose of brentuximab vedotin that can
      be combined with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin
      lymphoma that has come back (relapsed) or is not responding to treatment (refractory).
      Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in
      different ways by targeting certain cells. Chemotherapy drugs, such as ifosfamide,
      carboplatin, and etoposide, 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.
      Giving brentuximab vedotin together with an ifosfamide, carboplatin, and etoposide
      chemotherapy regimen may kill more cancer cells.
PRIMARY OBJECTIVES:

      I. To determine maximally tolerated dose of brentuximab vedotin that can be combined with
      ifosfamide, carboplatin and etoposide chemotherapy in patients with relapsed or refractory
      Hodgkin lymphoma.

      II. To gain a preliminary assessment of the efficacy of the above regimen.

      SECONDARY OBJECTIVES:

      I. To determine the safety and toxicity of the above regimen.

      II. To determine the ability to proceed to peripheral blood stem cell collection following
      the above regimen (the impact of above regimen on stem cell reserve).

      III. To assess the impact of this regimen on biomarkers from the microenvironment in Hodgkin
      lymphoma tumors.

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

      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 8;
      ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1
      hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease
      progression or unacceptable toxicity. Patients planning to go on to consolidative high-dose
      therapy (HDT) and autologous stem cell transplantation (ASCT) may undergo peripheral blood
      stem cell (PBSC) mobilization following the 2nd course of study therapy at the discretion of
      the treating physician.

      After completion of study treatment, patients are followed up every 3 months for 1 year and
      then every 6 months for 4 years.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy
time frame: Up to 28 days following the second course of chemotherapy, approximately 70 days
description: Will be defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
measure: Percentage of Patients That Achieve a Complete Remission Following Study Treatment
time frame: 3 weeks following the completion of chemotherapy
measure: 2 Year Overall Survival
time frame: Up to 2 years from initiation of study therapy.
measure: 2 Year Progression-free Survival
time frame: Up to 2 years from initiation of therapy.
arm group label: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
arm group type: Experimental
description: Patients receive brentuximab vedotin 1.2mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
arm group label: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group type: Experimental
description: Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
arm group label: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group type: Experimental
description: Patients receive brentuximab vedotin 1.5mg/kgIV over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative HDT and ASCT may undergo PBSC mobilization following the 2nd course of study therapy at the discretion of the treating physician.
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Given IV
arm group label: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
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: Carboplatin
description: Given IV
arm group label: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
other name: Blastocarb
other name: Carboplat
other name: Carboplatin Hexal
other name: Carboplatino
other name: Carbosin
other name: Carbosol
other name: Carbotec
other name: CBDCA
other name: Displata
other name: Ercar
other name: JM-8
other name: Nealorin
other name: Novoplatinum
other name: Paraplatin
other name: Paraplatin AQ
other name: Paraplatine
other name: Platinwas
other name: Ribocarbo
intervention type: Drug
intervention name: Etoposide
description: Given IV
arm group label: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
other name: Demethyl Epipodophyllotoxin Ethylidine Glucoside
other name: EPEG
other name: Lastet
other name: Toposar
other name: Vepesid
other name: VP 16-213
other name: VP-16
other name: VP-16-213
intervention type: Drug
intervention name: Ifosfamide
description: Given IV
arm group label: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
other name: Asta Z 4942
other name: Asta Z-4942
other name: Cyfos
other name: Holoxan
other name: Holoxane
other name: Ifex
other name: IFO
other name: IFO-Cell
other name: Ifolem
other name: Ifomida
other name: Ifomide
other name: Ifosfamidum
other name: Ifoxan
other name: IFX
other name: Iphosphamid
other name: Iphosphamide
other name: Iso-Endoxan
other name: Isoendoxan
other name: Isophosphamide
other name: Mitoxana
other name: MJF 9325
other name: MJF-9325
other name: Naxamide
other name: Seromida
other name: Tronoxal
other name: Z 4942
other name: Z-4942
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Phase I: Dose Escalation, Dose Level 1 (brentuximab 1.2mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase I: Dose Escalation, Dose Level 2 (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
arm group label: Phase II: Dose Expansion (brentuximab 1.5mg/kg, ifosfamide, carboplatin, etoposide)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajay Gopal
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Washington
investigator full name: Ajay Gopal
investigator title: Professor, Department of Medicine, Division of Oncology
mesh term: Lymphoma
mesh term: Hodgkin Disease
mesh term: Carboplatin
mesh term: Etoposide
mesh term: Etoposide phosphate
mesh term: Ifosfamide
mesh term: Isophosphamide mustard
mesh term: Brentuximab Vedotin
mesh term: Podophyllotoxin
mesh term: Antineoplastic Agents, Immunological
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoconjugates
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 