<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/NCT04502394</url>
  </required_header>
  <id_info>
    <org_study_id>KRT-232-111</org_study_id>
    <nct_id>NCT04502394</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL</brief_title>
  <official_title>An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia</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 study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with&#xD;
      acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic&#xD;
      Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 23, 2021</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL</measure>
    <time_frame>56 Days</time_frame>
    <description>Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)</measure>
    <time_frame>1 Year</time_frame>
    <description>Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL</measure>
    <time_frame>1 Year</time_frame>
    <description>Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Secondary Objective: Pharmacokinetic (PK) profile</measure>
    <time_frame>Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2</time_frame>
    <description>Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be estimated maximum concentration (Cmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Secondary Objective: Pharmacokinetic (PK) profile</measure>
    <time_frame>Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2</time_frame>
    <description>Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be area under the curve (AUC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Secondary Objective: Pharmacokinetic (PK) profile</measure>
    <time_frame>Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2</time_frame>
    <description>Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be half-life (T1/2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Secondary Objective: Pharmacokinetic (PK) profile</measure>
    <time_frame>Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2</time_frame>
    <description>Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be apparent clearance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1b Secondary Objective: Pharmacokinetic (PK) profile</measure>
    <time_frame>Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2</time_frame>
    <description>Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.</measure>
    <time_frame>2 Years</time_frame>
    <description>Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects</measure>
    <time_frame>2 Years</time_frame>
    <description>Endpoint/Outcome Measures: The proportion of subjects who achieve a PR or better at any time point while on study, as assessed by iwCLL Response Criteria</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">84</enrollment>
  <condition>Diffuse Large B Cell Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Non Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Cohort 1 (R/R DLBCL)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.&#xD;
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 (R/R CLL)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.&#xD;
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>KRT-232</intervention_name>
    <description>KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth</description>
    <arm_group_label>Cohort 1 (R/R DLBCL)</arm_group_label>
    <arm_group_label>Cohort 2 (R/R CLL)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>acalabrutinib</intervention_name>
    <description>acalabrutinib is a BTK inhibitor anticancer drug taken by mouth</description>
    <arm_group_label>Cohort 1 (R/R DLBCL)</arm_group_label>
    <arm_group_label>Cohort 2 (R/R CLL)</arm_group_label>
    <other_name>ACP-196</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cohort 1: Confirmed diagnosis of TP53wt DLBCL (WHO); R/R DLBCL after at least 2 prior&#xD;
             lines of treatment or 1 prior for patients who are ineligible for stem cell transplant&#xD;
&#xD;
          -  Cohort 2: Confirmed diagnosis of TP53wt CLL (iwCLL); R/R CLL after at least 1 prior&#xD;
             line of treatment&#xD;
&#xD;
          -  ECOG 0 to 2&#xD;
&#xD;
          -  Adequate hematologic, hepatic, and renal functions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with any MDM2 inhibitor&#xD;
&#xD;
          -  Prior treatment with any BTK inhibitor&#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_contact>
    <last_name>John Mei</last_name>
    <phone>650-542-0136</phone>
    <email>jmei@kartosthera.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Michael Yee</last_name>
    <phone>650-839-7361</phone>
    <email>myee@kartosthera.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Goshen Center for Cancer Care</name>
      <address>
        <city>Goshen</city>
        <state>Indiana</state>
        <zip>46526</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45221</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</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>Eastern Health - Box Hill Hospital</name>
      <address>
        <city>Box Hill</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Barwon Health</name>
      <address>
        <city>Geelong</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Perth Hospital</name>
      <address>
        <city>Perth</city>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Antwerp University Hospital (UZA)</name>
      <address>
        <city>Edegem</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Jessa Ziekenhuis</name>
      <address>
        <city>Hasselt</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Hospital (UZ) Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fakultni Nemocnice Hradec Kralove</name>
      <address>
        <city>Nový Hradec Králové</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Ostrava</name>
      <address>
        <city>Ostrava</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Vseobecna fakultni nemocnice v Praze</name>
      <address>
        <city>Prague</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes - Hôtel-Dieu</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centre Henri Becquerel</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHRU de Tours - Hôpital Bretonneau</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Riferimento Oncologico - Aviano</name>
      <address>
        <city>Aviano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori</name>
      <address>
        <city>Meldola</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>ASST Grande Ospedale Metropolitano Niguarda</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale San Raffaele</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Ricerche Cliniche di Verona s.r.l.</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Gachon University Gil Medical Center</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii</name>
      <address>
        <city>Gdansk</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Copernicus PL Sp. z o.o., Wojewodzkie Centrum Onkologii</name>
      <address>
        <city>Gdańsk</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach - Klinika Transplantacji Szpiku i Onkohematologii</name>
      <address>
        <city>Gliwice</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki Krakow - Oddzial Kliniczny Hematologii</name>
      <address>
        <city>Krakow</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Pratia MCM Krakow</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu</name>
      <address>
        <city>Wroclaw</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital de Braga</name>
      <address>
        <city>Braga</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria</name>
      <address>
        <city>Lisboa</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Champalimaud Cancer Center</name>
      <address>
        <city>Lisbon</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE</name>
      <address>
        <city>Porto</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar de Vila Nova de Gaia/Espinho EPE</name>
      <address>
        <city>Vila Nova de Gaia</city>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Kantonsspital St. Gallen</name>
      <address>
        <city>Saint Gallen</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>St James's University Hospital</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>King's College Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>August 3, 2022</last_update_submitted>
  <last_update_submitted_qc>August 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 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>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Lymphoma, Large B-Cell, Diffuse</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acalabrutinib</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/NCT04502394
org study id: KRT-232-111
nct id: NCT04502394
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with
      acalabrutinib for the treatment of adults with Diffuse Large B-Cell Lymphoma and Chronic
      Lymphocytic Leukemia. Participants must be relapsed/refractory (having failed prior therapy)
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: An Open-label, Phase 1b/2 Study of KRT-232 in combination with acalabrutinib in Subjects with B-cell Non-Hodgkin Lymphoma
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Objective Phase 1b:To determine the KRT-232 maximum tolerated dose/ maximum administered dose (MTD/MAD) and recommended Phase 2 Dose (RP2D) in combination with acalabrutinib in subjects with R/R DLBCL or R/R CLL
time frame: 56 Days
description: Endpoint/Outcome Measures: Dose-limiting toxicities will be used to establish the MTD/MAD of KRT-232 in combination with acalabrutinib. The Safety Review Committee will determine the RP2D based on safety data of the combination of KRT-232 and acalabrutinib.
measure: Primary Objective Phase 2: Cohort 1: To determine the complete response (CR)
time frame: 1 Year
description: Endpoint/Outcome Measures: Cohort 1: The proportion of subjects with CR as assessed by investigators per the Lugano Classification.
measure: Primary Objective Phase 2: Cohort 2: To determine the rate of CR/complete remission with incomplete hematologic recovery (CRi) rate in R/R CLL
time frame: 1 Year
description: Endpoint/Outcome Measures: Cohort 2: The proportion of subjects with CR/CRi as assessed by investigators per iwCLL Response Criteria.
measure: Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
time frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
description: Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be estimated maximum concentration (Cmax).
measure: Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
time frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
description: Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be area under the curve (AUC).
measure: Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
time frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
description: Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be half-life (T1/2).
measure: Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
time frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
description: Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameter from a single dose will be apparent clearance.
measure: Phase 1b Secondary Objective: Pharmacokinetic (PK) profile
time frame: Baseline, 1, 2, 4, 6 and 24 hours post dose on days 1 and 2 of cycle 1 (each cycle is 28 days); Baseline and 2 hours post dose on day 1 and 24 hours post dose on day 8 of cycle 2
description: Endpoint/Outcome Measures: Will be measured using liquid chromatography/tandem mass spectrometric method. Standard descriptive methods (point estimates and confidence intervals, scatterplots) will be used to summarize the baseline levels and the changes from baseline (i.e. after treatment). The individual PK parameters from a single dose will be apparent volume of distribution using non-compartmental or compartmental PK methods with the software WinNonlin.
measure: Phase 2 Secondary Objective: Cohort 1 (R/R DLBCL): To determine the overall response rate (ORR) for R/R DLBCL subjects.
time frame: 2 Years
description: Endpoint/Outcome Measures: The proportion of subjects who achieve a partial response (PR) or better at any time point while on study.
measure: Phase 2 Secondary Objective: Cohort 2 (R/R CLL): To determine the ORR for R/R CLL subjects
time frame: 2 Years
description: Endpoint/Outcome Measures: The proportion of subjects who achieve a PR or better at any time point while on study, as assessed by iwCLL Response Criteria
arm group label: Cohort 1 (R/R DLBCL)
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
arm group label: Cohort 2 (R/R CLL)
arm group type: Experimental
description: KRT-232 will be administered orally, once daily (QD), on days 1-7 in a 28-day cycle.
Acalabrutinib at 100 mg twice a day (BID) continuously starting on Day 1 in a 28-day cycle.
intervention type: Drug
intervention name: KRT-232
description: KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth
arm group label: Cohort 1 (R/R DLBCL)
arm group label: Cohort 2 (R/R CLL)
intervention type: Drug
intervention name: acalabrutinib
description: acalabrutinib is a BTK inhibitor anticancer drug taken by mouth
arm group label: Cohort 1 (R/R DLBCL)
arm group label: Cohort 2 (R/R CLL)
other name: ACP-196
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Mei
phone: 650-542-0136
email: jmei@kartosthera.com
last name: Michael Yee
phone: 650-839-7361
email: myee@kartosthera.com
facility: 
status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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facility: 
status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
facility: 
status: Recruiting
country: Australia
country: Belgium
country: Czechia
country: France
country: Italy
country: Korea, Republic of
country: Poland
country: Portugal
country: Switzerland
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Lymphoid
mesh term: Lymphoma, B-Cell
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Lymphoma, Large B-Cell, Diffuse
mesh term: Acalabrutinib