<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/NCT01700751</url>
  </required_header>
  <id_info>
    <org_study_id>201211047</org_study_id>
    <nct_id>NCT01700751</nct_id>
  </id_info>
  <brief_title>Brentuximab Vedotin Prevention of (GVHD) After Unrelated Allogeneic Stem Cell Transplantation</brief_title>
  <official_title>A Pilot Study of Brentuximab Vedotin in the Prevention of Graft-Versus-Host Disease (GVHD) After Unrelated Allogeneic Stem Cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</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 pilot clinical trial studies the safety and maximum tolerated dose of brentuximab&#xD;
      vedotin when given with tacrolimus and methotrexate after unrelated allogeneic donor stem&#xD;
      cell transplant in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or&#xD;
      myelodysplastic syndromes. The addition of brentuximab vedotin to tacrolimus and methotrexate&#xD;
      may result in a significant reduction of graft versus host disease in these patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 25, 2013</start_date>
  <completion_date type="Actual">November 21, 2016</completion_date>
  <primary_completion_date type="Actual">November 11, 2015</primary_completion_date>
  <phase>Phase 1</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>MTD of brentuximab vedotin when administered with a GVHD prophylaxis regimen</measure>
    <time_frame>37 days</time_frame>
    <description>Defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity; Hematologic DLT is defined as ANC &lt; 500/mm3 for three consecutive days beyond Day +21 that was determined by the investigator to be likely related to brentuximab vedotin.&#xD;
Non-hematologic DLT is defined as any grade 3 or higher non-hematologic toxicity that was determined by the investigator to be possibly, probably, or definitely related to brentuximab vedotin, with the following specific exceptions:&#xD;
Grade 3 or 4 nausea, vomiting, diarrhea, mucositis, or fatigue thought to be associated with conditioning regimens&#xD;
Grade 3 rash will only be considered a DLT for patients who have received two weeks of supportive care treatment with no improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of brentuximab vedotin when administered with a GVHD prophylaxis regimen</measure>
    <time_frame>100 days</time_frame>
    <description>Toxicities described and graded using CTCAE version 4.0; described by patient, type, and grade for each dose level; summarized by counts and percentage of patients in the corresponding categories</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of acute GVHD</measure>
    <time_frame>100 days</time_frame>
    <description>Proportion of all subjects who experience symptoms consistent with grade 2-4 acute GVHD; using the standard grading system adapted from the Glucksberg clinical stage and grade of acute GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of chronic GVHD</measure>
    <time_frame>2 years</time_frame>
    <description>Proportion of all subjects who experience symptoms consistent with chronic GVHD; assessment will begin after Day 100 using the NIH consensus criteria for diagnosis and staging of chronic GVHD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>2 years</time_frame>
    <description>Duration from the time of transplant to time of first progression, death, relapse after complete response, or the date the patient was last known to be in remission; estimated with Kaplan-Meier methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival.</measure>
    <time_frame>2 years</time_frame>
    <description>Duration from the time of transplant to death or last follow-up; estimated with Kaplan-Meier methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-year non-relapse mortality rate</measure>
    <time_frame>1 year</time_frame>
    <description>Defined as the percentage of patients dying from etiologies other than disease relapse; estimated with Kaplan-Meier methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-year non-relapse mortality rate</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as the percentage of patients dying from etiologies other than disease relapse; estimated with Kaplan-Meier methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>1-year disease relapse rate</measure>
    <time_frame>1 year</time_frame>
    <description>Defined as the percentage of patients who have disease relapse; estimated with Kaplan-Meier methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2-year disease relapse rate</measure>
    <time_frame>2 years</time_frame>
    <description>Defined as the percentage of patients who have disease relapse; estimated with Kaplan-Meier methods.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Leukemia, Acute Myeloid</condition>
  <condition>Leukemia, Lymphoblastic,Acute</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>Dose Level 0 (starting dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>brentuximab vedotin 0.3mg/kg, given IV on Days 7, 28, 49 &amp; 70</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>brentuximab vedotin 0.6mg/kg, given IV on Days 7, 28, 49 &amp; 70</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>brentuximab vedotin 1.2mg/kg, given IV on Days 7, 28, 49 &amp; 70</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>brentuximab vedotin 1.8mg/kg, given IV on Days 7, 28, 49 &amp; 70</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Dose Level</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The first 3 patients will not receive brentuximab vedotin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>brentuximab vedotin</intervention_name>
    <arm_group_label>Dose Level 0 (starting dose)</arm_group_label>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
    <other_name>Adcetris</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must be scheduled to undergo stem cell transplantation for one of the&#xD;
             following diagnoses:&#xD;
&#xD;
               -  acute myeloid leukemia (AML) in CR1 (first complete remission, CR or CRi) or CR2&#xD;
                  (second complete remission, CR or CRi),&#xD;
&#xD;
               -  acute lymphoblastic leukemia (ALL) in CR1 or CR2 (CR or CRi)&#xD;
&#xD;
               -  myelodysplastic syndrome (MDS) without progression to AML.&#xD;
&#xD;
               -  Chronic myelogenous leukemia (CML)&#xD;
&#xD;
               -  Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD)&#xD;
&#xD;
               -  Chronic lymphocytic leukemia (CLL)&#xD;
&#xD;
               -  Multiple myeloma (MM)&#xD;
&#xD;
          -  Patients must be the recipient of unrelated donor peripheral blood stem cell products.&#xD;
             Mismatches at both antigen and allele level will be eligible. Match must be 6 or 7 out&#xD;
             of 8 loci (HLA A, B, C, and DRB1).&#xD;
&#xD;
          -  Patient must receive any one of the following conditioning regimens: total body&#xD;
             radiation (single or fractionated dose)/cyclophosphamide, busulfan/ cyclophosphamide,&#xD;
             or fludarabine/busulfan/lymphocyte immune globulin (ATGAM/thymo).&#xD;
&#xD;
          -  Patient must be ≥ 18 years and ≤ 70 years of age.&#xD;
&#xD;
          -  Patient must have an ECOG performance status ≤ 2 or Karnofsky performance scale ≥ 60%&#xD;
&#xD;
          -  Patient must have CD34+ stem cells ≥ 2x106/kg (actual body weight of the recipient)&#xD;
             available for transplantation.&#xD;
&#xD;
          -  Patient must have appropriate organ function as defined below (this criterion should&#xD;
             be met on screening and on the day of the first dose of brentuximab vedotin (as&#xD;
             assessed prior to dosing)):&#xD;
&#xD;
               -  Total bilirubin ≤ 2.0 x IULN&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN&#xD;
&#xD;
               -  Serum creatinine ≤ 2.0 x IULN&#xD;
&#xD;
               -  Estimated Creatinine Clearance &gt; 30 ml/min&#xD;
&#xD;
               -  Cardiac ejection fraction &gt; 40%&#xD;
&#xD;
               -  DLCO/VA &gt; 40%&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while participating in this study, she must inform her treating physician&#xD;
             immediately.&#xD;
&#xD;
          -  Patient must be able to understand and willing to sign an IRB approved written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient must not have had prior exposure to brentuximab vedotin.&#xD;
&#xD;
          -  Patient must not have a history of other malignancy that has not been in remission for&#xD;
             at least 3 years, with the exception of basal non-melanoma skin cancer which were&#xD;
             treated with local resection only or intraepithelial lesions or carcinoma in situ of&#xD;
             the cervix or prostate that has been curatively treated.&#xD;
&#xD;
          -  Patient must not be receiving any other investigational agents.&#xD;
&#xD;
          -  Patient must not have active CNS involvement.&#xD;
&#xD;
          -  Patient must not have a history of allergic reactions attributed to compounds of&#xD;
             similar chemical or biologic composition to brentuximab vedotin or other agents used&#xD;
             in the study.&#xD;
&#xD;
          -  Patients must not have had previous radiation therapy to the mediastinum or lungs.&#xD;
&#xD;
          -  Patient must not have an uncontrolled inter-current illness including, but not limited&#xD;
             to, ongoing or active infection, symptomatic congestive heart failure, unstable angina&#xD;
             pectoris, cardiac arrhythmia, active pulmonary diseases, or psychiatric illness/social&#xD;
             situations that would limit compliance with study requirements (this criterion should&#xD;
             be met on screening and on the day of but prior to first dose of brentuximab vedotin).&#xD;
&#xD;
          -  Patient must not be pregnant and/or breastfeeding.&#xD;
&#xD;
          -  Patient must not be known to be HIV-positive on combination antiretroviral therapies.&#xD;
&#xD;
          -  Patient must not have had a previous allogeneic or syngeneic transplant. Prior&#xD;
             autologous transplant is allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Schroeder, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>September 18, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>April 12, 2019</last_update_submitted>
  <last_update_submitted_qc>April 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brentuximab Vedotin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01700751
org study id: 201211047
nct id: NCT01700751
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This pilot clinical trial studies the safety and maximum tolerated dose of brentuximab
      vedotin when given with tacrolimus and methotrexate after unrelated allogeneic donor stem
      cell transplant in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or
      myelodysplastic syndromes. The addition of brentuximab vedotin to tacrolimus and methotrexate
      may result in a significant reduction of graft versus host disease in these patients.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTD of brentuximab vedotin when administered with a GVHD prophylaxis regimen
time frame: 37 days
description: Defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity; Hematologic DLT is defined as ANC < 500/mm3 for three consecutive days beyond Day +21 that was determined by the investigator to be likely related to brentuximab vedotin.
Non-hematologic DLT is defined as any grade 3 or higher non-hematologic toxicity that was determined by the investigator to be possibly, probably, or definitely related to brentuximab vedotin, with the following specific exceptions:
Grade 3 or 4 nausea, vomiting, diarrhea, mucositis, or fatigue thought to be associated with conditioning regimens
Grade 3 rash will only be considered a DLT for patients who have received two weeks of supportive care treatment with no improvement.
measure: Safety and tolerability of brentuximab vedotin when administered with a GVHD prophylaxis regimen
time frame: 100 days
description: Toxicities described and graded using CTCAE version 4.0; described by patient, type, and grade for each dose level; summarized by counts and percentage of patients in the corresponding categories
measure: Rate of acute GVHD
time frame: 100 days
description: Proportion of all subjects who experience symptoms consistent with grade 2-4 acute GVHD; using the standard grading system adapted from the Glucksberg clinical stage and grade of acute GVHD
measure: Rate of chronic GVHD
time frame: 2 years
description: Proportion of all subjects who experience symptoms consistent with chronic GVHD; assessment will begin after Day 100 using the NIH consensus criteria for diagnosis and staging of chronic GVHD
measure: Progression-free survival
time frame: 2 years
description: Duration from the time of transplant to time of first progression, death, relapse after complete response, or the date the patient was last known to be in remission; estimated with Kaplan-Meier methods.
measure: Overall survival.
time frame: 2 years
description: Duration from the time of transplant to death or last follow-up; estimated with Kaplan-Meier methods.
measure: 1-year non-relapse mortality rate
time frame: 1 year
description: Defined as the percentage of patients dying from etiologies other than disease relapse; estimated with Kaplan-Meier methods.
measure: 2-year non-relapse mortality rate
time frame: 2 years
description: Defined as the percentage of patients dying from etiologies other than disease relapse; estimated with Kaplan-Meier methods.
measure: 1-year disease relapse rate
time frame: 1 year
description: Defined as the percentage of patients who have disease relapse; estimated with Kaplan-Meier methods.
measure: 2-year disease relapse rate
time frame: 2 years
description: Defined as the percentage of patients who have disease relapse; estimated with Kaplan-Meier methods.
arm group label: Dose Level 0 (starting dose)
arm group type: Experimental
description: brentuximab vedotin 0.3mg/kg, given IV on Days 7, 28, 49 & 70
arm group label: Dose Level 1
arm group type: Experimental
description: brentuximab vedotin 0.6mg/kg, given IV on Days 7, 28, 49 & 70
arm group label: Dose Level 2
arm group type: Experimental
description: brentuximab vedotin 1.2mg/kg, given IV on Days 7, 28, 49 & 70
arm group label: Dose Level 3
arm group type: Experimental
description: brentuximab vedotin 1.8mg/kg, given IV on Days 7, 28, 49 & 70
arm group label: Control Dose Level
arm group type: No Intervention
description: The first 3 patients will not receive brentuximab vedotin.
intervention type: Drug
intervention name: brentuximab vedotin
arm group label: Dose Level 0 (starting dose)
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
other name: Adcetris
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Mark Schroeder, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Myeloid, Acute
mesh term: Myelodysplastic Syndromes
mesh term: Brentuximab Vedotin
sharing ipd: No