<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/NCT01703949</url>
  </required_header>
  <id_info>
    <org_study_id>7808</org_study_id>
    <secondary_id>NCI-2012-01696</secondary_id>
    <secondary_id>7808</secondary_id>
    <secondary_id>RG1713010</secondary_id>
    <nct_id>NCT01703949</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma</brief_title>
  <official_title>A Pilot Study of Weekly Brentuximab Vedotin or Brentuximab Vedotin Plus Nivolumab Every 3 Weeks in Patients With CD30+ Malignancies Refractory to Every ≥ 3 Week Brentuximab Vedotin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Washington</source>
  <oversight_info>
    <has_dmc>No</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 II pilot trial studies how well brentuximab vedotin with or without nivolumab&#xD;
      works in treating patients with CD30+ lymphoma that has come back after a period of&#xD;
      improvement or does not respond to treatment. Biological therapies, such as brentuximab&#xD;
      vedotin, may stimulate the immune system in different ways and stop cancer cells from&#xD;
      growing. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor&#xD;
      cells to grow and spread. Giving brentuximab vedotin with or without nivolumab may work&#xD;
      better in treating patients with CD30+ lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OUTLINE:&#xD;
&#xD;
      ARM A (CLOSED TO ACCRUAL): Patients receive brentuximab vedotin intravenously (IV) over 30&#xD;
      minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM B: Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60&#xD;
      minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 3-5 weeks, every 3 months&#xD;
      for 1 year, and then every 6 months for 4 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 20, 2013</start_date>
  <completion_date type="Anticipated">September 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall response rate as measured by the Cheson 2007 criteria</measure>
    <time_frame>Up to 5 weeks after completion of study treatment</time_frame>
    <description>No formal statistical measures will be pre-specified. This protocol will be deemed a &quot;success&quot; if the absolute response rate in this group of patients is &gt;= 20%.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Recurrent Hodgkin Lymphoma</condition>
  <condition>Recurrent Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Hodgkin Lymphoma</condition>
  <condition>Refractory Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Arm A (brentuximab vedotin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (brentuximab vedotin, nivolumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brentuximab Vedotin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A (brentuximab vedotin)</arm_group_label>
    <arm_group_label>Arm B (brentuximab vedotin, nivolumab)</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>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm A (brentuximab vedotin)</arm_group_label>
    <arm_group_label>Arm B (brentuximab vedotin, nivolumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm B (brentuximab vedotin, nivolumab)</arm_group_label>
    <other_name>BMS-936558</other_name>
    <other_name>MDX-1106</other_name>
    <other_name>NIVO</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>Opdivo</other_name>
    <other_name>CMAB819</other_name>
    <other_name>Nivolumab Biosimilar CMAB819</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Relapsed or refractory CD30+ lymphoma that has either achieved &lt; PR to brentuximab&#xD;
             vedotin (minimum of 2 cycles), progressed while receiving brentuximab vedotin, or&#xD;
             progressed within 6 months of the last dose of brentuximab vedotin&#xD;
&#xD;
          -  Documented expression of CD30 on tumor cells&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt; 1,000/uL&#xD;
&#xD;
          -  Platelets &gt; 50,000/uL&#xD;
&#xD;
          -  Serum creatinine &lt; 1.5 mg/dL OR creatinine clearance &gt; 60 mL/min&#xD;
&#xD;
          -  Bilirubin &lt; 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) &lt; 2.5 x ULN&#xD;
&#xD;
          -  Measurable disease by computed tomography (CT) or similar (e.g. magnetic resonance&#xD;
             imaging [MRI]) criteria (&gt; 1.5 cm). (Patients with cutaneous lymphoma only require&#xD;
             measurable disease by Olsen Criteria)&#xD;
&#xD;
          -  Age &gt;= 18 yrs at the time of the first dose of study drug&#xD;
&#xD;
          -  Resolution of all non-hematologic brentuximab vedotin-related and nivolumab-related&#xD;
             adverse events (AEs) to &lt; Grade 2&#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 at least 2 cycles of chemotherapy on study&#xD;
&#xD;
          -  Expected survival if untreated of &gt; 90 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior transplant within 100 days&#xD;
&#xD;
          -  Radioimmunotherapy within 12 weeks&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) or hepatitis B positivity or prior&#xD;
             progressive multifocal leukoencephalopathy (PML)&#xD;
&#xD;
          -  Active infection or other medical condition which would preclude treatment in the&#xD;
             opinion of the principal investigator; this would include a corrected diffusing&#xD;
             capacity of the lungs for carbon monoxide (DLCO) of &lt; 60% predicted or symptomatic&#xD;
             interstitial lung disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status &gt; 2&#xD;
&#xD;
          -  Known active central nervous system (CNS) involvement&#xD;
&#xD;
          -  Peripheral neuropathy &gt; grade 1 if due to brentuximab vedotin or any peripheral&#xD;
             neuropathy &gt; grade 2&#xD;
&#xD;
          -  Intolerance to brentuximab vedotin&#xD;
&#xD;
          -  Concurrent use of other anti-cancer agents or experimental treatments&#xD;
&#xD;
          -  No current or prior autoimmune disease with the exception of vitiligo and autoimmune&#xD;
             alopecia (Arm B only)&#xD;
&#xD;
          -  Pregnancy or breastfeeding; (females of childbearing potential must have a negative&#xD;
             serum or urine beta human chorionic gonadotropin [beta-hCG] pregnancy test result&#xD;
             within 7 days prior to the first dose of brentuximab vedotin; females with false&#xD;
             positive results and documented verification that the patient is not pregnant are&#xD;
             eligible for participation; females of non-childbearing potential are those who are&#xD;
             postmenopausal greater than 1 year or who have had a bilateral tubal ligation or&#xD;
             hysterectomy; females of childbearing potential and males who have partners of&#xD;
             childbearing potential must agree to use 2 effective contraceptive methods during the&#xD;
             study and for 6 months following the last dose of brentuximab vedotin or 6 months&#xD;
             following the last dose of nivolumab, whichever is later)&#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 K. Gopal</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ajay K. Gopal</last_name>
    <phone>206-606-2037</phone>
    <email>agopal@uw.edu</email>
  </overall_contact>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Ajay K. Gopal</last_name>
      <phone>206-606-2037</phone>
      <email>agopal@uw.edu</email>
    </contact>
    <investigator>
      <last_name>Ajay K. Gopal</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>April 28, 2023</last_update_submitted>
  <last_update_submitted_qc>April 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Brentuximab Vedotin</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoconjugates</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01703949
org study id: 7808
secondary id: NCI-2012-01696
secondary id: 7808
secondary id: RG1713010
nct id: NCT01703949
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II pilot trial studies how well brentuximab vedotin with or without nivolumab
      works in treating patients with CD30+ lymphoma that has come back after a period of
      improvement or does not respond to treatment. Biological therapies, such as brentuximab
      vedotin, may stimulate the immune system in different ways and stop cancer cells from
      growing. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor
      cells to grow and spread. Giving brentuximab vedotin with or without nivolumab may work
      better in treating patients with CD30+ lymphoma.
OUTLINE:

      ARM A (CLOSED TO ACCRUAL): Patients receive brentuximab vedotin intravenously (IV) over 30
      minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the
      absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60
      minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 3-5 weeks, every 3 months
      for 1 year, and then every 6 months for 4 years.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate as measured by the Cheson 2007 criteria
time frame: Up to 5 weeks after completion of study treatment
description: No formal statistical measures will be pre-specified. This protocol will be deemed a "success" if the absolute response rate in this group of patients is >= 20%.
arm group label: Arm A (brentuximab vedotin)
arm group type: Experimental
description: Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
arm group label: Arm B (brentuximab vedotin, nivolumab)
arm group type: Experimental
description: Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Brentuximab Vedotin
description: Given IV
arm group label: Arm A (brentuximab vedotin)
arm group label: Arm B (brentuximab vedotin, nivolumab)
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: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm A (brentuximab vedotin)
arm group label: Arm B (brentuximab vedotin, nivolumab)
intervention type: Biological
intervention name: Nivolumab
description: Given IV
arm group label: Arm B (brentuximab vedotin, nivolumab)
other name: BMS-936558
other name: MDX-1106
other name: NIVO
other name: ONO-4538
other name: Opdivo
other name: CMAB819
other name: Nivolumab Biosimilar CMAB819
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajay K. Gopal
role: Principal Investigator
affiliation: Fred Hutch/University of Washington Cancer Consortium
last name: Ajay K. Gopal
phone: 206-606-2037
email: agopal@uw.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Hodgkin Disease
mesh term: Recurrence
mesh term: Antineoplastic Agents, Immunological
mesh term: Nivolumab
mesh term: Brentuximab Vedotin
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoconjugates