<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/NCT04402541</url>
  </required_header>
  <id_info>
    <org_study_id>CTX-001</org_study_id>
    <nct_id>NCT04402541</nct_id>
  </id_info>
  <brief_title>Study of CB-5339 in Acute Myeloid Leukemia or Myelodysplastic Syndrome</brief_title>
  <official_title>A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profiles of CB-5339 in Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Intermediate or High Risk Myelodysplastic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cleave Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cleave Therapeutics, Inc.</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 is a multicenter, open-label Phase 1 study of orally administered CB-5339 in&#xD;
      participants with R/R AML or participants with R/R intermediate- to high-risk MDS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in&#xD;
      participants with R/R AML or participants with R/R intermediate- to high-risk MDS. The study&#xD;
      will include two parts:1) a Dose Escalation phase in participants with R/R AML, or R/R&#xD;
      intermediate- to high-risk MDS and 2) a Dose Expansion phase in participants with R/R AML for&#xD;
      whom there is no standard of care therapy available that is likely to lead to disease&#xD;
      remission. Additional cohorts for participants with R/R intermediate- to high-risk MDS&#xD;
      following hypomethylating agents or other AML cohorts may be added at a later time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 8, 2020</start_date>
  <completion_date type="Actual">July 23, 2023</completion_date>
  <primary_completion_date type="Actual">July 23, 2023</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>Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).</measure>
    <time_frame>28 Days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Define the MTD and/or RP2D and schedule for CB-5339</measure>
    <time_frame>28 Days</time_frame>
    <description>Incidence and nature of DLTs with CB-5339 monotherapy for MTD determination. All available safety, efficacy and PK, for RP2D determination</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax)</measure>
    <time_frame>Day 1 and Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach peak plasma concentration (Tmax)</measure>
    <time_frame>Day 1 and Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration time curve (AUC0-t)</measure>
    <time_frame>Day 1 and Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t½)</measure>
    <time_frame>Day 1 and Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio</measure>
    <time_frame>Day 1 and Day 4</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor effects</measure>
    <time_frame>End of each cycle (cycle is 28 days)</time_frame>
    <description>CR/CRi rate at the RP2D in participants with R/R AML, as assessed by the investigator, based on 2017 ELN response criteria.&#xD;
Objective response rate (ORR) at the RP2D in participants with R/R AML, as assessed by the investigator based on 2017 ELN response criteria.&#xD;
DoCR in participants with R/R AML who attain CR or CRi</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Acute Myeloid Leukemia, in Relapse</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>CB-5339</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Orally administered CB-5339</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CB-5339</intervention_name>
    <description>25mg and 75mg capsules</description>
    <arm_group_label>CB-5339</arm_group_label>
    <other_name>CB-5339 Tosylate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female and ≥ 18 years of age at the time of signing the consent form&#xD;
&#xD;
          2. One of the following advanced hematologic malignancies including:&#xD;
&#xD;
               -  Relapsed or refractory AML as defined by 2016 WHO criteria and are not candidates&#xD;
                  for curative therapies such as allogeneic hematopoietic cell transplant or for&#xD;
                  whom there is no standard of care therapy available that is likely to lead to&#xD;
                  disease remission according the investigator&#xD;
&#xD;
               -  MDS high-very high risk by the revised international scoring system for&#xD;
                  evaluating prognosis in myelodysplastic syndromes that is recurrent or refractory&#xD;
                  or the participant is intolerant to established therapy known to provide clinical&#xD;
                  benefit for their condition (e.g., relapsed following treatment with&#xD;
                  hypomethylating agent or lack of response after &gt; 4 cycles), according to&#xD;
                  treating physician. Potential participants who meet the criteria for intermediate&#xD;
                  risk may be considered with approval by the medical monitor if the participant&#xD;
                  has severe cytopenia(s) and/or elevated bone marrow blast counts.&#xD;
&#xD;
          3. Adequate organ function defined as:&#xD;
&#xD;
               -  Serum creatinine ≤1.5 mg/dL or an estimated glomerular filtration rate of ≥60&#xD;
                  mL/min as calculated by the Cockcroft-Gault glomerular filtration rate equation&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) unless considered due to&#xD;
                  Gilbert's disease or leukemic disease&#xD;
&#xD;
               -  Aspartate aminotransferase (AST) ≤3 × the ULN; alanine aminotransferase (ALT) ≤3&#xD;
                  × the ULN. Levels of AST and/or ALT ≤5 × the ULN may be acceptable for&#xD;
                  participants with known leukemic involvement of the liver after discussion with&#xD;
                  the study medical monitor&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.&#xD;
&#xD;
          5. Contraceptive use by men or women should be consistent with local regulations&#xD;
             regarding the methods of contraception for those participating in clinical studies. If&#xD;
             of childbearing potential, agree to use an effective barrier method of birth control&#xD;
             (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy during the&#xD;
             study and 90 days after the last dose of CB-5339. Female participants of childbearing&#xD;
             potential need a negative serum or urine pregnancy test within 7 days of study&#xD;
             enrollment. Non-childbearing is defined as ≥ 1 year postmenopausal or surgically&#xD;
             sterilized&#xD;
&#xD;
          6. Capable of giving signed informed consent as described in Appendix 1 which includes&#xD;
             compliance with the requirements and restrictions listed in the informed consent form&#xD;
             (ICF) and in this protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic&#xD;
             leukemia/retinoic acid receptor alpha (PML-RARA).&#xD;
&#xD;
          2. Participants with clinical symptoms suggestive of active central nervous system (CNS)&#xD;
             leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if&#xD;
             there is a clinical suspicion of CNS involvement by leukemia during screening.&#xD;
&#xD;
          3. Participants with immediately life-threatening, severe complications of leukemia such&#xD;
             as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated&#xD;
             intravascular coagulation.&#xD;
&#xD;
          4. Concomitant malignancy, requiring active treatment, except for basal-cell or squamous&#xD;
             cell carcinoma of the skin, carcinoma-in-situ of the uterine cervix, or localized&#xD;
             prostate cancer.&#xD;
&#xD;
             • Adjuvant therapy for breast cancer or prostate cancer is allowed.&#xD;
&#xD;
          5. Active, uncontrolled, systemic infection or severe localized infection during&#xD;
             screening or prior to Cycle 1 Day 1 (C1D1; unless considered due to tumor by the&#xD;
             investigator).&#xD;
&#xD;
             • Note, participants receiving prophylactic anti-infectives are allowed on study.&#xD;
&#xD;
          6. Known human immunodeficiency virus (HIV) infection with CD4+ T cell counts &lt;350&#xD;
             cells/μL, initiation of antiretroviral therapy within 4 weeks before C1D1, or acquired&#xD;
             immunodeficiency syndrome (AIDS)-related infection within 12 months before C1D1.&#xD;
&#xD;
          7. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with viral load above the&#xD;
             limit of quantification&#xD;
&#xD;
          8. Major cardiac abnormalities as defined but not limited to the following: uncontrolled&#xD;
             angina or unstable life-threatening arrhythmias, history of myocardial infarction&#xD;
             within 12 weeks prior to Baseline, Class 3 or higher New York Heart Association (NYHA)&#xD;
             congestive heart failure, or left ventricular ejection fraction (LVEF) &lt;45% as&#xD;
             measured by echocardiogram (ECHO) within 28 days of C1D1&#xD;
&#xD;
          9. Persistent (3 consecutive ECGs performed ≥5 minutes apart) prolongation of the&#xD;
             corrected QT interval by Fredericia's method (QTcF) to &gt; 480 msec&#xD;
&#xD;
         10. Gastrointestinal conditions that may interfere with the absorption of&#xD;
             orally-administered drugs including but not limited to short gut syndrome,&#xD;
             gastroparesis, inflammatory bowel disease, or acute pancreatitis.&#xD;
&#xD;
         11. Any other severe, acute, or chronic medical or psychiatric condition, or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or CB-5339&#xD;
             administration, may interfere with the informed consent process and/or with compliance&#xD;
             with the requirements of the study, may interfere with the interpretation of the study&#xD;
             results and, in the Investigator's opinion, or would make the participant&#xD;
             inappropriate for entry into this study&#xD;
&#xD;
         12. A condition that is expected to require concomitant use of any medication listed as&#xD;
             prohibited while on study.&#xD;
&#xD;
         13. Known hypersensitivity to any components of CB-5339.&#xD;
&#xD;
         14. Use of chemotherapy (except hydroxyurea), radiation or monoclonal antibodies within 14&#xD;
             days or 5 half-lives for small molecule inhibitors prior to first dose of CB-5339&#xD;
&#xD;
         15. Participants who have undergone a hematopoietic cell transplant (HCT) within 100 days&#xD;
             of the first dose of CB-5339, or participants on immunosuppressive therapy post-HCT at&#xD;
             the time of screening, use of calcineurin inhibitors within 4 weeks prior to first&#xD;
             dose of CB-5339, or with clinically significant graft-versus-host disease (GVHD).&#xD;
&#xD;
             • Note: The use of topical steroids or &lt;10mg oral prednisone for ongoing skin GVHD is&#xD;
             permitted.&#xD;
&#xD;
         16. Major surgery within 4 weeks prior to first dose of CB-5339. Participant must have&#xD;
             recovered from surgery and be without current complications of infection or dehiscence&#xD;
&#xD;
         17. Enrollment in other clinical trials unless approved by Medical Monitor&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Scott Harris</last_name>
    <role>Study Chair</role>
    <affiliation>Cleave Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KU Clinical Research Center</name>
      <address>
        <city>Fairway</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornel Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Francis Hospital Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>29607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic, Case Comprehensive Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Cancer</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Hospital, Sydney, NSW</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Epworth Healthcare</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3002</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haematology Clinical Trials Unit, Royal Perth Hospital</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>August 30, 2023</last_update_submitted>
  <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</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/NCT04402541
org study id: CTX-001
nct id: NCT04402541
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in
      participants with R/R AML or participants with R/R intermediate- to high-risk MDS.
This is a multicenter, open-label Phase 1 study of orally administered CB-5339 in
      participants with R/R AML or participants with R/R intermediate- to high-risk MDS. The study
      will include two parts:1) a Dose Escalation phase in participants with R/R AML, or R/R
      intermediate- to high-risk MDS and 2) a Dose Expansion phase in participants with R/R AML for
      whom there is no standard of care therapy available that is likely to lead to disease
      remission. Additional cohorts for participants with R/R intermediate- to high-risk MDS
      following hypomethylating agents or other AML cohorts may be added at a later time.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
time frame: 28 Days
measure: Define the MTD and/or RP2D and schedule for CB-5339
time frame: 28 Days
description: Incidence and nature of DLTs with CB-5339 monotherapy for MTD determination. All available safety, efficacy and PK, for RP2D determination
measure: Peak plasma concentration (Cmax)
time frame: Day 1 and Day 4
measure: Time to reach peak plasma concentration (Tmax)
time frame: Day 1 and Day 4
measure: Area under the plasma concentration time curve (AUC0-t)
time frame: Day 1 and Day 4
measure: Elimination half-life (t½)
time frame: Day 1 and Day 4
measure: Accumulation ratio
time frame: Day 1 and Day 4
measure: Antitumor effects
time frame: End of each cycle (cycle is 28 days)
description: CR/CRi rate at the RP2D in participants with R/R AML, as assessed by the investigator, based on 2017 ELN response criteria.
Objective response rate (ORR) at the RP2D in participants with R/R AML, as assessed by the investigator based on 2017 ELN response criteria.
DoCR in participants with R/R AML who attain CR or CRi
arm group label: CB-5339
arm group type: Experimental
description: Orally administered CB-5339
intervention type: Drug
intervention name: CB-5339
description: 25mg and 75mg capsules
arm group label: CB-5339
other name: CB-5339 Tosylate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Scott Harris
role: Study Chair
affiliation: Cleave Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome