xml: <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/NCT06007911</url>
    </required_header>
    <id_info>
      <org_study_id>IIT-GURU-VEN-NAV-AML</org_study_id>
      <nct_id>NCT06007911</nct_id>
    </id_info>
    <brief_title>Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia</brief_title>
    <official_title>Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Medical College of Wisconsin</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Medical College of Wisconsin</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 an open-label phase I study designed to evaluate the safety of venetoclax-navitoclax&#xD;
        with cladribine-based salvage therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The primary objective of the study is to determine a maximum-tolerated dose (MTD) combination&#xD;
        of venetoclax-navitoclax with cladribine-based salvage therapy. Subjects will be entered&#xD;
        sequentially to each dose level. For each dose level, if none of the first three subjects at&#xD;
        that level experiences a dose-limiting toxicity (DLT), new subjects may be entered at the&#xD;
        next higher dose level. If one of three subjects experience a DLT, up to three more subjects&#xD;
        are to be treated at that same dose level. If none of the additional three subjects at that&#xD;
        dose level experiences a DLT, new subjects may be entered at the next higher dose level.&#xD;
        However, if one or more of the additional three subjects experience a DLT, then no further&#xD;
        subjects are to be started at that dose level and either de-escalate one level or if the&#xD;
        preceding dose is already completed then that dose is the MTD. The MTD will be defined as the&#xD;
        highest dose level at which none of the first three treated subjects, or no more than one of&#xD;
        the first six treated subjects, experiences a DLT.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">February 2027</completion_date>
    <primary_completion_date type="Anticipated">October 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Maximum Tolerated Dose of Navitoclax for the Cladribine-Low Dose Cytarabine Backbone</measure>
      <time_frame>Up to three years</time_frame>
      <description>The MTD will be defined as the highest dose level of navitoclax at which none of the first three treated subjects, or no more than one of the first six treated subjects, experiences a DLT.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Tolerated Dose for Navitoclax for the CLAG-M Backbone</measure>
      <time_frame>Up to three years</time_frame>
      <description>The MTD will be defined as the highest dose level of navitoclax at which none of the first three treated subjects, or no more than one of the first six treated subjects, experiences a DLT.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose-limiting Toxicities for Cladribine-Low Dose Cytarabine Backbone</measure>
      <time_frame>Up to three years</time_frame>
      <description>The number of dose-limiting toxicities before obtaining maximum tolerated dose.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose-limiting Toxicities for CLAG-M Backbone</measure>
      <time_frame>Up to three years</time_frame>
      <description>The number of dose-limiting toxicities before obtaining maximum tolerated dose.</description>
    </primary_outcome>
    <number_of_arms>10</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Relapsed Adult AML</condition>
    <condition>Refractory AML</condition>
    <arm_group>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level -1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 0</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and granulocyte colony-stimulating factor (G-CSF).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Navitoclax Dose Level -1</intervention_name>
      <description>25 mg by mouth on days 1-7.</description>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level -1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>ABT-263</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Navitoclax Dose Level 0</intervention_name>
      <description>50 mg by mouth on days 1-10.</description>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 0</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>ABT-263</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Navitoclax Dose Level 1</intervention_name>
      <description>75 mg by mouth on days 1-10.</description>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>ABT-263</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Navitoclax Dose Level 2</intervention_name>
      <description>100 mg by mouth on days 1-10.</description>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 2</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>ABT-263</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Venetoclax Dose Level -1</intervention_name>
      <description>400 mg by mouth on days 1-7.</description>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level -1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>Venclexta</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Venetoclax Dose Levels 0 to 2</intervention_name>
      <description>400 mg by mouth on days 1-14.</description>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 0</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 2</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>Venclexta</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cladribine</intervention_name>
      <description>5 mg/m^2 intravenously days 1-5.</description>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level -1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 0</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 2</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>Mavenclad</other_name>
      <other_name>Leustatin DSC</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cytarabine (Cladribine Low Dose Cytarabine Backbone)</intervention_name>
      <description>20 mg/m^2 subcutaneous days 1-10.</description>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level -1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 0</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 1</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Level 2</arm_group_label>
      <arm_group_label>Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)</arm_group_label>
      <other_name>ara-C</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cytarabine (CLAG-M Backbone)</intervention_name>
      <description>2 g/m^2 intravenously days 1-5.</description>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <other_name>ara-C</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mitoxantrone</intervention_name>
      <description>10 mg/m^2 intravenously days 1-3.</description>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <other_name>Novantrone</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Granulocyte Colony-Stimulating Factor</intervention_name>
      <description>300 mcg subcutaneously days 1-5.</description>
      <arm_group_label>CLAG-M Backbone Level -1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 0</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 1</arm_group_label>
      <arm_group_label>CLAG-M Backbone Level 2</arm_group_label>
      <arm_group_label>CLAG-M Backbone Maximum Tolerated Dose</arm_group_label>
      <other_name>G-CSF</other_name>
      <other_name>filgrastim</other_name>
      <other_name>Neupogen</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female subjects 18 years or older.&#xD;
  &#xD;
            2. Patients must have a diagnosis of morphologically documented AML or secondary AML from&#xD;
               prior conditions, such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm&#xD;
               (MPN), MDS/MPN, chronic myelomonocytic leukemia (CMML) or therapy-related AML (t-AML),&#xD;
               as defined by the World Health Organization (WHO) criteria.&#xD;
  &#xD;
            3. Relapsed or refractory to at least one prior line of therapy.&#xD;
  &#xD;
            4. Previous therapy with venetoclax.&#xD;
  &#xD;
            5. Eastern Cooperative Oncology Group (ECOG) performance status of:&#xD;
  &#xD;
                 1. 0-3 for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).&#xD;
  &#xD;
                 2. 0-2 for Arm B (i.e., CLAG-M backbone arm).&#xD;
  &#xD;
            6. Left ventricular ejection fraction (LVEF) of:&#xD;
  &#xD;
                 1. LVEF ≥35% for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).&#xD;
  &#xD;
                 2. LVEF ≥45% for Arm B (i.e., CLAG-M backbone arm).&#xD;
  &#xD;
            7. Creatinine clearance (creatinine clearance) as calculated by the Cockroft-Gault&#xD;
               formula, of:&#xD;
  &#xD;
                 1. CrCl ≥ 30 mL/min for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).&#xD;
  &#xD;
                 2. CrCl ≥ 40 mL/min for Arm B (i.e., CLAG-M backbone arm).&#xD;
  &#xD;
            8. Clinical laboratory values within the following parameters:&#xD;
  &#xD;
                 1. Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) unless&#xD;
                    attributable to underlying leukemia. Patient with total bilirubin &gt; 1.5 ×&#xD;
                    institutional ULN may enroll if direct bilirubin ≤ 1.5 × institutional ULN of the&#xD;
                    direct bilirubin.&#xD;
  &#xD;
                 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 ×&#xD;
                    institutional ULN, unless attributable to underlying leukemia.&#xD;
  &#xD;
                 3. White blood cell (WBC) count &lt; 25,000/µL before Cycle 1, Day 1 of therapy (Note:&#xD;
                    Hydroxyurea, cytarabine or leukapheresis may be used to meet this criterion.)&#xD;
  &#xD;
                 4. Platelet count of at least 20,000/µL before Cycle 1, Day 1 of therapy (Note:&#xD;
                    Platelet transfusion can be used to meet this criterion.)&#xD;
  &#xD;
            9. Female subjects who:&#xD;
  &#xD;
                 1. Are postmenopausal for at least one year before the screening visit, OR&#xD;
  &#xD;
                 2. Are surgically sterile, OR&#xD;
  &#xD;
                 3. If they are of childbearing potential:&#xD;
  &#xD;
               i. Agree to practice one highly effective method and one additional effective&#xD;
               (barrier) method of contraception, at the same time, from the time of signing the&#xD;
               informed consent through four months after the last dose of study drug (female and&#xD;
               male condoms should not be used together), OR ii. Agree to practice true abstinence,&#xD;
               when this is in line with the preferred and usual lifestyle of the subject. (periodic&#xD;
               abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods],&#xD;
               withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of&#xD;
               contraception).&#xD;
  &#xD;
           10. Male subjects, even if surgically sterilized (i.e., status post vasectomy), who:&#xD;
  &#xD;
                 1. Agree to practice effective barrier contraception during the entire study&#xD;
                    treatment period from the time of signing the informed consent through and&#xD;
                    through four months after the last dose of study drug (female and male condoms&#xD;
                    should not be used together), OR&#xD;
  &#xD;
                 2. Agree to practice true abstinence, when this is in line with the preferred and&#xD;
                    usual lifestyle of the subject. (periodic abstinence [e.g., calendar, ovulation,&#xD;
                    symptothermal, post-ovulation methods for the female partner] withdrawal,&#xD;
                    spermicides only, and lactational amenorrhea are not acceptable methods of&#xD;
                    contraception.)&#xD;
  &#xD;
           11. Ability to understand a written informed consent document, and the willingness to sign&#xD;
               it.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Acute promyelocytic leukemia.&#xD;
  &#xD;
            2. Prior therapy with B-cell lymphoma-extra large (BCL-XL) inhibitor.&#xD;
  &#xD;
            3. Treatment with systemic antineoplastic therapy within 14 days or five half-lives from&#xD;
               the last dose - whichever is sooner - before Cycle 1, Day 1 of therapy. Radiation&#xD;
               within 14 days before Cycle 1, Day 1 of therapy. The use of hydroxyurea/cytarabine for&#xD;
               leukoreduction is permitted.&#xD;
  &#xD;
            4. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T-cell&#xD;
               therapy (CAR-T cell) within 60 days of enrollment&#xD;
  &#xD;
            5. Current systemic treatment with strong or moderate Cytochrome P4503A (CYP3A) inducers&#xD;
               within 7 days prior to Cycle 1, Day 1 of therapy.&#xD;
  &#xD;
            6. Presence of another active malignancy requiring systemic treatment within the last 12&#xD;
               months, except for localized cancers that have been adequately treated.&#xD;
  &#xD;
            7. Known HIV positive patients who DO NOT meet the following criteria:&#xD;
  &#xD;
                 1. Cluster of differentiation (CD) 4 count &gt; 350 cells/mm^3.&#xD;
  &#xD;
                 2. Undetectable viral load.&#xD;
  &#xD;
                 3. Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents.&#xD;
  &#xD;
                 4. No history of AIDS-defining opportunistic infections.&#xD;
  &#xD;
            8. Known hepatitis B surface antigen seropositive or active hepatitis C infection. Note:&#xD;
               Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of&#xD;
               negative hepatitis B surface antigen and negative hepatitis B surface antibody) must&#xD;
               have an undetectable hepatitis B viral load. Patients who have positive hepatitis C&#xD;
               antibody may be included if they have an undetectable hepatitis C viral load.&#xD;
  &#xD;
            9. Female subjects who are both lactating and breastfeeding or of childbearing potential&#xD;
               who have a positive serum test during screening.&#xD;
  &#xD;
           10. Female subjects who intend to donate eggs (ova) during the course of the study or four&#xD;
               months after receiving their last dose of the study drug(s).&#xD;
  &#xD;
           11. Male subjects who intend to donate sperm during the course of this study or four&#xD;
               months after receiving their last dose of the study drug(s).&#xD;
  &#xD;
           12. Has consumed grapefruit, grapefruit products, Seville oranges (including marmalade&#xD;
               containing Seville oranges) or star fruit from three days prior to Cycle 1, Day 1 to&#xD;
               throughout the study treatment.&#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>Guru Subramanian Guru Murthy, MD, MS</last_name>
      <role>Principal Investigator</role>
      <affiliation>Medical College of Wisconsin</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Medical College of Wisconsin Cancer Center Clinical Trials Office</last_name>
      <phone>866-680-0505</phone>
      <phone_ext>8900</phone_ext>
      <email>cccto@mcw.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Froedtert Hospital &amp; the Medical College of Wisconsin</name>
        <address>
          <city>Milwaukee</city>
          <state>Wisconsin</state>
          <zip>53226</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Guru Subramanian Guru Murthy, MD, MS</last_name>
        <email>gmurthy@mcw.edu</email>
      </contact>
      <investigator>
        <last_name>Guru Subramanian Guru Murthy, MD, MS</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
      <investigator_full_name>Guru Subramanian Guru Murthy</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>Acute Myeloid Leukemia</keyword>
    <keyword>AML</keyword>
    <keyword>Venetoclax</keyword>
    <keyword>Navitoclax</keyword>
    <keyword>cladribine-based salvage therapy</keyword>
    <keyword>CLAG-M</keyword>
    <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>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cytarabine</mesh_term>
      <mesh_term>Venetoclax</mesh_term>
      <mesh_term>Mitoxantrone</mesh_term>
      <mesh_term>Cladribine</mesh_term>
      <mesh_term>Navitoclax</mesh_term>
      <mesh_term>Lenograstim</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06007911
  org study id: IIT-GURU-VEN-NAV-AML
  nct id: NCT06007911
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is an open-label phase I study designed to evaluate the safety of venetoclax-navitoclax
        with cladribine-based salvage therapy.
  The primary objective of the study is to determine a maximum-tolerated dose (MTD) combination
        of venetoclax-navitoclax with cladribine-based salvage therapy. Subjects will be entered
        sequentially to each dose level. For each dose level, if none of the first three subjects at
        that level experiences a dose-limiting toxicity (DLT), new subjects may be entered at the
        next higher dose level. If one of three subjects experience a DLT, up to three more subjects
        are to be treated at that same dose level. If none of the additional three subjects at that
        dose level experiences a DLT, new subjects may be entered at the next higher dose level.
        However, if one or more of the additional three subjects experience a DLT, then no further
        subjects are to be started at that dose level and either de-escalate one level or if the
        preceding dose is already completed then that dose is the MTD. The MTD will be defined as the
        highest dose level at which none of the first three treated subjects, or no more than one of
        the first six treated subjects, experiences a DLT.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Maximum Tolerated Dose of Navitoclax for the Cladribine-Low Dose Cytarabine Backbone
  time frame: Up to three years
  description: The MTD will be defined as the highest dose level of navitoclax at which none of the first three treated subjects, or no more than one of the first six treated subjects, experiences a DLT.
  measure: Maximum Tolerated Dose for Navitoclax for the CLAG-M Backbone
  time frame: Up to three years
  description: The MTD will be defined as the highest dose level of navitoclax at which none of the first three treated subjects, or no more than one of the first six treated subjects, experiences a DLT.
  measure: Dose-limiting Toxicities for Cladribine-Low Dose Cytarabine Backbone
  time frame: Up to three years
  description: The number of dose-limiting toxicities before obtaining maximum tolerated dose.
  measure: Dose-limiting Toxicities for CLAG-M Backbone
  time frame: Up to three years
  description: The number of dose-limiting toxicities before obtaining maximum tolerated dose.
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level -1
  arm group type: Experimental
  description: Dose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 0
  arm group type: Experimental
  description: This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 1
  arm group type: Experimental
  description: This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 2
  arm group type: Experimental
  description: This is a regimen of navitoclax, venetoclax, cladribine and cytarabine.
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  arm group type: Experimental
  description: The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.
  arm group label: CLAG-M Backbone Level -1
  arm group type: Experimental
  description: Dose level -1 will be considered only if there are dose-limiting toxicities at dose level 0. This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.
  arm group label: CLAG-M Backbone Level 0
  arm group type: Experimental
  description: This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and granulocyte colony-stimulating factor (G-CSF).
  arm group label: CLAG-M Backbone Level 1
  arm group type: Experimental
  description: This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.
  arm group label: CLAG-M Backbone Level 2
  arm group type: Experimental
  description: This is a regimen of navitoclax, venetoclax, cladribine, cytarabine, mitoxantrone and G-CSF.
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group type: Experimental
  description: The MTD is the highest dose level at which no more than 1 of 6 treated participants, experiences a dose-limiting toxicity.
  intervention type: Drug
  intervention name: Navitoclax Dose Level -1
  description: 25 mg by mouth on days 1-7.
  arm group label: CLAG-M Backbone Level -1
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level -1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: ABT-263
  intervention type: Drug
  intervention name: Navitoclax Dose Level 0
  description: 50 mg by mouth on days 1-10.
  arm group label: CLAG-M Backbone Level 0
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 0
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: ABT-263
  intervention type: Drug
  intervention name: Navitoclax Dose Level 1
  description: 75 mg by mouth on days 1-10.
  arm group label: CLAG-M Backbone Level 1
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: ABT-263
  intervention type: Drug
  intervention name: Navitoclax Dose Level 2
  description: 100 mg by mouth on days 1-10.
  arm group label: CLAG-M Backbone Level 2
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 2
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: ABT-263
  intervention type: Drug
  intervention name: Venetoclax Dose Level -1
  description: 400 mg by mouth on days 1-7.
  arm group label: CLAG-M Backbone Level -1
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level -1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: Venclexta
  intervention type: Drug
  intervention name: Venetoclax Dose Levels 0 to 2
  description: 400 mg by mouth on days 1-14.
  arm group label: CLAG-M Backbone Level 0
  arm group label: CLAG-M Backbone Level 1
  arm group label: CLAG-M Backbone Level 2
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 0
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 2
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: Venclexta
  intervention type: Drug
  intervention name: Cladribine
  description: 5 mg/m^2 intravenously days 1-5.
  arm group label: CLAG-M Backbone Level -1
  arm group label: CLAG-M Backbone Level 0
  arm group label: CLAG-M Backbone Level 1
  arm group label: CLAG-M Backbone Level 2
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level -1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 0
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 2
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: Mavenclad
  other name: Leustatin DSC
  intervention type: Drug
  intervention name: Cytarabine (Cladribine Low Dose Cytarabine Backbone)
  description: 20 mg/m^2 subcutaneous days 1-10.
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level -1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 0
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 1
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Level 2
  arm group label: Cladribine-Low Dose Cytarabine Backbone Dose Maximum Tolerated Dose (MTD)
  other name: ara-C
  intervention type: Drug
  intervention name: Cytarabine (CLAG-M Backbone)
  description: 2 g/m^2 intravenously days 1-5.
  arm group label: CLAG-M Backbone Level -1
  arm group label: CLAG-M Backbone Level 0
  arm group label: CLAG-M Backbone Level 1
  arm group label: CLAG-M Backbone Level 2
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  other name: ara-C
  intervention type: Drug
  intervention name: Mitoxantrone
  description: 10 mg/m^2 intravenously days 1-3.
  arm group label: CLAG-M Backbone Level -1
  arm group label: CLAG-M Backbone Level 0
  arm group label: CLAG-M Backbone Level 1
  arm group label: CLAG-M Backbone Level 2
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  other name: Novantrone
  intervention type: Drug
  intervention name: Granulocyte Colony-Stimulating Factor
  description: 300 mcg subcutaneously days 1-5.
  arm group label: CLAG-M Backbone Level -1
  arm group label: CLAG-M Backbone Level 0
  arm group label: CLAG-M Backbone Level 1
  arm group label: CLAG-M Backbone Level 2
  arm group label: CLAG-M Backbone Maximum Tolerated Dose
  other name: G-CSF
  other name: filgrastim
  other name: Neupogen
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Guru Subramanian Guru Murthy, MD, MS
  role: Principal Investigator
  affiliation: Medical College of Wisconsin
  last name: Medical College of Wisconsin Cancer Center Clinical Trials Office
  phone: 866-680-0505
  phone ext: 8900
  email: cccto@mcw.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Medical College of Wisconsin
  investigator full name: Guru Subramanian Guru Murthy
  investigator title: Assistant Professor
  mesh term: Leukemia
  mesh term: Leukemia, Myeloid
  mesh term: Leukemia, Myeloid, Acute
  mesh term: Cytarabine
  mesh term: Venetoclax
  mesh term: Mitoxantrone
  mesh term: Cladribine
  mesh term: Navitoclax
  mesh term: Lenograstim
  sharing ipd: No