<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/NCT04485260</url>
  </required_header>
  <id_info>
    <org_study_id>KRT-232-109</org_study_id>
    <nct_id>NCT04485260</nct_id>
  </id_info>
  <brief_title>An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib</brief_title>
  <official_title>An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Ruxolitinib in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (Post-PV-MF), Or Post-Essential Thrombocythemia MF (Post ET-MF) Who Have a Suboptimal Response to Ruxolitinib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kartos Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kartos Therapeutics, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have&#xD;
      a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary&#xD;
      objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in&#xD;
      combination with ruxolitinib.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 28, 2021</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2022</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>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>For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib</measure>
    <time_frame>15 months</time_frame>
    <description>Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>For Phase 2:To determine the spleen volume reduction (SVR) at Week 24</measure>
    <time_frame>6 months after last patient enrolled</time_frame>
    <description>The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine spleen response</measure>
    <time_frame>43 months</time_frame>
    <description>The proportion of subjects achieving ≥35% SVR at any time point from Baseline while on study, as assessed by MRI (or by CT scan for applicable subjects)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)</measure>
    <time_frame>43 months</time_frame>
    <description>The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Myelofibrosis</condition>
  <arm_group>
    <arm_group_label>Part A, Arm 1, Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KRT-232</intervention_name>
    <description>administered by mouth</description>
    <arm_group_label>Part A, Arm 1, Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>administered by mouth</description>
    <arm_group_label>Part A, Arm 1, Cohort 1</arm_group_label>
    <other_name>Jakafi</other_name>
    <other_name>Jakavi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating&#xD;
             physician according to the World Health Organization (WHO)&#xD;
&#xD;
          -  Treatment with ruxolitinib for ≥18 weeks prior to study entry, and on a stable dose of&#xD;
             ruxolitinib in the 8 weeks prior to study entry&#xD;
&#xD;
          -  Spleen ≥5 cm palpable below the LLCM or ≥450 cm3 by MRI or CT&#xD;
&#xD;
          -  Patients must have at least 2 symptoms with a score of at least 1 on the MFSAF v4.0&#xD;
&#xD;
          -  ECOG performance status of 0 to 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are positive for TP53 mutations&#xD;
&#xD;
          -  Documented disease progression or clinical deterioration any time while on ruxolitinib&#xD;
             treatment&#xD;
&#xD;
          -  Patients who have had a documented spleen response to ruxolitinib.&#xD;
&#xD;
          -  Prior splenectomy&#xD;
&#xD;
          -  Prior MDM2 inhibitor therapy or p53-directed therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>John Mei</last_name>
    <phone>650-542-0136</phone>
    <email>jmei@kartosthera.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>John Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Dr. Georgi Stranski</name>
      <address>
        <city>Pleven</city>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Saint Ivan Rilski Hospital</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Mutiprofile Hospital Alexandrovska</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU de Caen</name>
      <address>
        <city>Caen</city>
        <state>Cedex 9</state>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Chu Angers</name>
      <address>
        <city>Angers</city>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier du Mans</name>
      <address>
        <city>Le Mans</city>
        <zip>72000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Institut Paoli-Calmettes</name>
      <address>
        <city>Marseille</city>
        <zip>13009</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU Saint Eloi</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Louis</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU Tours - Hôpital Bretonneau</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Aachen Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Department für Innere Medizin Universitätsklinik und Poliklinik für Innere Medizin IV Hämatologie/Onkologie</name>
      <address>
        <city>Halle</city>
        <zip>6120</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Jena</name>
      <address>
        <city>Jena</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz III. Med. Klinik und Poliklinik</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Stauferklinikum Schwäbisch Gmünd</name>
      <address>
        <city>Mutlangen</city>
        <zip>73557</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Shamir Medical Center ( Assaf Harofeh)</name>
      <address>
        <city>Zerifin</city>
        <zip>7033001</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Bologna University Hospital, Institute of Hematology</name>
      <address>
        <city>Bologna</city>
        <zip>340136</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universita degli Studi di Catania</name>
      <address>
        <city>Catania</city>
        <zip>95124</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Florence</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Istituto Tumori della Romagna (IRST)</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Ospedale di Circolo e Fondazione MacchiASST Sette Laghi</name>
      <address>
        <city>Varese</city>
        <zip>21100</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Oddział Kliniczny Hematologii Szpitala Uniwersyteckiego w Krakowie</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Szpital Wojewódzki w Opolu Sp zooOddzial Kliniczny Hematologii</name>
      <address>
        <city>Opole</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>d'Hebron University Hospital in Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Germans Trias i Pujol</name>
      <address>
        <city>Barcelona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Gran Canaria Doctor Negrin</name>
      <address>
        <city>Las Palmas De Gran Canaria</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital de Dia Quiron Zaragoza</name>
      <address>
        <city>Zaragoza</city>
        <zip>50012</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Bulgaria</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>May 5, 2022</last_update_submitted>
  <last_update_submitted_qc>May 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>navtemadlin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycythemia Vera</mesh_term>
    <mesh_term>Primary Myelofibrosis</mesh_term>
    <mesh_term>Polycythemia</mesh_term>
    <mesh_term>Thrombocytosis</mesh_term>
    <mesh_term>Thrombocythemia, Essential</mesh_term>
  </condition_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/NCT04485260
org study id: KRT-232-109
nct id: NCT04485260
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1b/2 study of KRT-232 combined with ruxolitinib in subjects with MF who have
      a suboptimal response after at least 18 weeks of treatment with ruxolitinib. The primary
      objective of the study is to determine a recommended phase 2 dose (RP2D) of KRT 232 in
      combination with ruxolitinib.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: For Phase 1: To determine the KRT-232 RP2D in combination with ruxolitinib
time frame: 15 months
description: Dose limiting toxicities will be used to establish the MTD of KRT-232 in combination with ruxolitinib. Subsequently, RP2D will be based on safety and efficacy data of the combination.
measure: For Phase 2:To determine the spleen volume reduction (SVR) at Week 24
time frame: 6 months after last patient enrolled
description: The proportion of subjects achieving SVR of ≥ 35% at Week 24 by MRI/CT scan
measure: To determine spleen response
time frame: 43 months
description: The proportion of subjects achieving ≥35% SVR at any time point from Baseline while on study, as assessed by MRI (or by CT scan for applicable subjects)
measure: To determine the change in Total Symptom Score (TSS) based Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0)
time frame: 43 months
description: The percentage change in TSS as measured by the MFSAF v4.0 at any time point from Baseline while on study
arm group label: Part A, Arm 1, Cohort 1
arm group type: Experimental
description: KRT-232 by mouth once daily for Days 1-7, off treatment for Days 8-28 (28 day cycle)
intervention type: Drug
intervention name: KRT-232
description: administered by mouth
arm group label: Part A, Arm 1, Cohort 1
intervention type: Drug
intervention name: Ruxolitinib
description: administered by mouth
arm group label: Part A, Arm 1, Cohort 1
other name: Jakafi
other name: Jakavi
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: John Mei
phone: 650-542-0136
email: jmei@kartosthera.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
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status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Australia
country: Bulgaria
country: France
country: Germany
country: Israel
country: Italy
country: Poland
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Polycythemia Vera
mesh term: Primary Myelofibrosis
mesh term: Polycythemia
mesh term: Thrombocytosis
mesh term: Thrombocythemia, Essential