<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/NCT03826992</url>
  </required_header>
  <id_info>
    <org_study_id>V2-MA-1801</org_study_id>
    <nct_id>NCT03826992</nct_id>
  </id_info>
  <brief_title>Venetoclax Combined With Vyxeos (CPX-351) for Participants With Relapsed or Refractory Acute Leukemia</brief_title>
  <official_title>A Phase I Study of Venetoclax Combined With Vyxeos (CPX-351) for Children, Adolescents and Young Adults With Relapsed or Refractory Acute Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</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 study evaluates the safety and tolerability of combining venetoclax with Vyxeos&#xD;
      (CPX-351) in pediatric and young adult patients with acute leukemia that has come back or not&#xD;
      responded to treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-institution Phase I pilot study designed to test the safety and tolerability&#xD;
      of combining venetoclax with Vyxeos (CPX-351, cytarabine and daunorubicin liposome) for the&#xD;
      treatment of relapsed/refractory acute leukemia in young patients. Subjects will receive a&#xD;
      single course of study therapy consisting of daily, oral venetoclax at an assigned dose level&#xD;
      with a 3-day ramp-up to target dose and Vyxeos administered intravenously at the established&#xD;
      dose on Days 1, 3, and 5. In addition to safety and tolerability, the overall response rate&#xD;
      to these therapies will be estimated. Pharmacokinetic (PK) analysis will also be conducted to&#xD;
      define the drug clearance of venetoclax in this combination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 27, 2018</start_date>
  <completion_date type="Anticipated">January 2026</completion_date>
  <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility of combining venetoclax and Vyxeos (dose limiting toxicities)</measure>
    <time_frame>28 days</time_frame>
    <description>If 2 or more participants have dose limiting toxicities at a given dose level, the maximum tolerated dose will have been exceeded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Treatment related toxicities</measure>
    <time_frame>60 days</time_frame>
    <description>Number of related adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease response</measure>
    <time_frame>42 days</time_frame>
    <description>Estimate of overall response rate (ORR) defined as (CR/CRi/CRp).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cancer therapeutics-related cardiac dysfunction (CTRCD) in patients who have previously received anthracyclines</measure>
    <time_frame>60 days</time_frame>
    <description>Measured by echocardiogram (ECHO)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">21</enrollment>
  <condition>Leukemia</condition>
  <arm_group>
    <arm_group_label>Venetoclax and Vyxeos combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Venetoclax will be given orally on Days per the assigned dose level. A single course consisting of 3 doses of Vyxeos and 7-21 doses of venetoclax depending on the assigned dose level will be administered to participants in this study. Vyxeos will be administered by central venous catheter over 90 minutes on Day 1, 3, and 5.&#xD;
Venetoclax is given daily by mouth per assigned dose level.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vyxeos</intervention_name>
    <description>Vyxeos Dose: daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 administered via intravenous infusion over 90 minutes on Days 1, 3, and 5.</description>
    <arm_group_label>Venetoclax and Vyxeos combination</arm_group_label>
    <other_name>cytarabine and daunorubicin liposome, CPX-351</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Venetoclax Dose:&#xD;
Dose Level 0 - weight based daily dosing for 21 days&#xD;
Dose Level -1 - weight based daily dosing for 14 days&#xD;
Dose Level -2- weight based daily dosing for 10 days&#xD;
Dose Level -3- weight based daily dosing for 7 days</description>
    <arm_group_label>Venetoclax and Vyxeos combination</arm_group_label>
    <other_name>Venclexta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ages 1-39 years&#xD;
&#xD;
          -  Diagnosis of one of the following:&#xD;
&#xD;
               -  Acute myeloid leukemia (AML)&#xD;
&#xD;
               -  Acute undifferentiated leukemia (AUL)&#xD;
&#xD;
               -  Mixed phenotype acute leukemia (MPAL)&#xD;
&#xD;
               -  T-cell acute lymphoblastic leukemia (T ALL)&#xD;
&#xD;
               -  Early thymocyte precursor (ETP) ALL&#xD;
&#xD;
               -  KMT2A-rearranged ALL&#xD;
&#xD;
          -  Disease status&#xD;
&#xD;
               -  Relapsed/Refractory AML, MPAL and AUL&#xD;
&#xD;
               -  Relapsed/Refractory KMT2A-rearranged ALL, T-cell ALL, ETP ALL&#xD;
&#xD;
          -  Karnofsky/ Lanksy performance level score of greater than or equal to 50 percent&#xD;
&#xD;
          -  Prior therapy requirements&#xD;
&#xD;
               -  Fully recovered from acute toxicities of Hematopoietic Stem Cell Transplant&#xD;
                  (HSCT) or Anthracycline Exposure&#xD;
&#xD;
               -  14 days must have elapsed since the completion of systemic cytotoxic therapy&#xD;
                  other than hydroxyurea, decitabine or azacitidine&#xD;
&#xD;
               -  2 weeks must have elapsed for local palliative radiotherapy (RT); 6 months must&#xD;
                  have elapsed if prior craniospinal RT or if 50% radiation of pelvis, and at least&#xD;
                  6 weeks must have elapsed if other substantial bone marrow radiation&#xD;
&#xD;
          -  Adequate renal, liver, cardiac and central nervous system (CNS) function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of one of the following:&#xD;
&#xD;
               -  Acute Promyelocytic Leukemia (APML)&#xD;
&#xD;
               -  Acute leukemia with CNS status 3 involvement&#xD;
&#xD;
               -  Philadelphia chromosome positive leukemia (Ph+ ALL, MPAL, or AUL)&#xD;
&#xD;
               -  Fanconi Anemia, Shwachman-Diamond syndrome, or any other bone marrow failure&#xD;
                  syndrome or DNA repair disorder&#xD;
&#xD;
               -  Wilson's Disease or other copper-metabolism disorder&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Uncontrolled infection&#xD;
&#xD;
          -  Received greater than 13.6 Gray (Gy) prior radiation to the mediastinum&#xD;
&#xD;
          -  Unable to swallow tablets&#xD;
&#xD;
          -  Receipt of growth factors within 7 days prior to enrollment&#xD;
&#xD;
          -  Currently receiving another investigational drug&#xD;
&#xD;
          -  Currently receiving anti-cancer agents (with the exception of intrathecal (IT) agents&#xD;
             or hydroxyurea)&#xD;
&#xD;
          -  Unable to comply with the safety monitoring requirements of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Perentesis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Site Pulblic Contact</last_name>
    <phone>513-636-2799</phone>
    <email>cancer@cchmc.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>513-636-2799</phone>
      <email>cancer@cchmc.org</email>
    </contact>
    <investigator>
      <last_name>John Perentesis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Laura Agresta, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.cincinnatichildrens.org/research/divisions/c/cbdi/default/</url>
    <description>Cincinnati Children's Cancer and Blood Diseases Institute</description>
  </link>
  <link>
    <url>http://www.cincinnatichildrens.org/research/divisions/o/oncology/default/</url>
    <description>Cincinnati Children's Hospital Oncology Division</description>
  </link>
  <link>
    <url>http://www.cincinnatichildrens.org/service/l/leukemia-lymphoma/clinical-trials/</url>
    <description>Leukemia and Lymphoma Program</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>relapsed</keyword>
  <keyword>refractory</keyword>
  <keyword>Vyxeos</keyword>
  <keyword>Venetoclax</keyword>
  <keyword>acute myeloid leukemia</keyword>
  <keyword>acute myeloid leukemia, childhood</keyword>
  <keyword>mixed-lineage leukemia (MLL)</keyword>
  <keyword>AML</keyword>
  <keyword>CPX-351</keyword>
  <keyword>Venclexta</keyword>
  <keyword>Histone-lysine N-methyltransferase 2A (KmT2A)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Daunorubicin</mesh_term>
    <mesh_term>Venetoclax</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/NCT03826992
org study id: V2-MA-1801
nct id: NCT03826992
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study evaluates the safety and tolerability of combining venetoclax with Vyxeos
      (CPX-351) in pediatric and young adult patients with acute leukemia that has come back or not
      responded to treatment.
This is a single-institution Phase I pilot study designed to test the safety and tolerability
      of combining venetoclax with Vyxeos (CPX-351, cytarabine and daunorubicin liposome) for the
      treatment of relapsed/refractory acute leukemia in young patients. Subjects will receive a
      single course of study therapy consisting of daily, oral venetoclax at an assigned dose level
      with a 3-day ramp-up to target dose and Vyxeos administered intravenously at the established
      dose on Days 1, 3, and 5. In addition to safety and tolerability, the overall response rate
      to these therapies will be estimated. Pharmacokinetic (PK) analysis will also be conducted to
      define the drug clearance of venetoclax in this combination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Feasibility of combining venetoclax and Vyxeos (dose limiting toxicities)
time frame: 28 days
description: If 2 or more participants have dose limiting toxicities at a given dose level, the maximum tolerated dose will have been exceeded.
measure: Treatment related toxicities
time frame: 60 days
description: Number of related adverse events
measure: Disease response
time frame: 42 days
description: Estimate of overall response rate (ORR) defined as (CR/CRi/CRp).
measure: Cancer therapeutics-related cardiac dysfunction (CTRCD) in patients who have previously received anthracyclines
time frame: 60 days
description: Measured by echocardiogram (ECHO)
arm group label: Venetoclax and Vyxeos combination
arm group type: Experimental
description: Venetoclax will be given orally on Days per the assigned dose level. A single course consisting of 3 doses of Vyxeos and 7-21 doses of venetoclax depending on the assigned dose level will be administered to participants in this study. Vyxeos will be administered by central venous catheter over 90 minutes on Day 1, 3, and 5.
Venetoclax is given daily by mouth per assigned dose level.
intervention type: Drug
intervention name: Vyxeos
description: Vyxeos Dose: daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 administered via intravenous infusion over 90 minutes on Days 1, 3, and 5.
arm group label: Venetoclax and Vyxeos combination
other name: cytarabine and daunorubicin liposome, CPX-351
intervention type: Drug
intervention name: Venetoclax
description: Venetoclax Dose:
Dose Level 0 - weight based daily dosing for 21 days
Dose Level -1 - weight based daily dosing for 14 days
Dose Level -2- weight based daily dosing for 10 days
Dose Level -3- weight based daily dosing for 7 days
arm group label: Venetoclax and Vyxeos combination
other name: Venclexta
criteria: 
gender: All
minimum age: 1 Year
maximum age: 39 Years
healthy volunteers: No
last name: John Perentesis, MD
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
last name: Site Pulblic Contact
phone: 513-636-2799
email: cancer@cchmc.org
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
url: http://www.cincinnatichildrens.org/research/divisions/c/cbdi/default/
description: Cincinnati Children's Cancer and Blood Diseases Institute
url: http://www.cincinnatichildrens.org/research/divisions/o/oncology/default/
description: Cincinnati Children's Hospital Oncology Division
url: http://www.cincinnatichildrens.org/service/l/leukemia-lymphoma/clinical-trials/
description: Leukemia and Lymphoma Program
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Cytarabine
mesh term: Daunorubicin
mesh term: Venetoclax
sharing ipd: No