<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/NCT04454658</url>
  </required_header>
  <id_info>
    <org_study_id>M20-247</org_study_id>
    <secondary_id>2020-001225-32</secondary_id>
    <nct_id>NCT04454658</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability Study of Oral ABBV-744 Tablet Alone or in Combination With Oral Ruxolitinib Tablet or Oral Navitoclax Tablet in Adult Participants With Myelofibrosis</brief_title>
  <official_title>A Phase 1b Study Of ABBV-744 Alone Or In Combination With Ruxolitinib Or Navitoclax In Subjects With Myelofibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body.&#xD;
      MF disturbs the body's normal production of blood cells, causing extensive scarring in the&#xD;
      bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The&#xD;
      purpose of this study is to see how safe and tolerable ABBV-744 is, when given alone, and in&#xD;
      combination with ruxolitinib or navitoclax, for adult participants with MF.&#xD;
&#xD;
      ABBV-744 is an investigational drug being developed for the treatment of MF. The study has 4&#xD;
      segments - A, B, C, and D. In Segment A, the safe dosing regimen of ABBV-744 is identified&#xD;
      and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of&#xD;
      ABBV-744 with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis&#xD;
      of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.&#xD;
&#xD;
      In Segment A, participants will receive different doses and schedules of oral ABBV-744 tablet&#xD;
      to identify safe dosing regimen. Additional participants will be enrolled at the identified&#xD;
      monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and&#xD;
      ABBV-744 will be given as &quot;add-on&quot; therapy. In Segment C, participants will receive ABBV-744&#xD;
      and oral navitoclax. In Segment D, participants will receive ABBV-744 and ruxolitinib.&#xD;
      Participants will receive treatment until disease progression or the participants are not&#xD;
      able to tolerate the study drugs.&#xD;
&#xD;
      There may be higher treatment burden for participants in this trial compared to their&#xD;
      standard of care. Participants will attend regular visits during the study at a hospital or&#xD;
      clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow&#xD;
      tests, checking for side effects, and completing questionnaires.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 11, 2020</start_date>
  <completion_date type="Anticipated">July 26, 2024</completion_date>
  <primary_completion_date type="Anticipated">July 26, 2024</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>Percentage of Participants With Adverse Events</measure>
    <time_frame>Up to Approximately 1 year from start of study</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage Of Participants Who Achieve Spleen Volume Reduction Of 35% Or Greater (SVR35)</measure>
    <time_frame>Up To Week 24</time_frame>
    <description>Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Maximum observed plasma concentration (Cmax) of ABBV-744.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time To Cmax (Tmax) Of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>The amount of time taken to reach Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>AUC of ABBV-744 will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-Life (t1/2) Of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Half-life of ABBV-744 will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio Of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Pharmacokinetic parameters will include accumulation ratio of ABBV-744.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/F) Of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>CL/F of ABBV-744 will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume Of Distribution (Vd/F) Of ABBV-744</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Vd/F of ABBV-744 will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Of Participants With &gt;= 50% Reduction In Total Symptom Score (TSS)</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Week 24</time_frame>
    <description>ORR is defined as the sum of rates of partial remission (PR) or better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) Of Navitoclax</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time To Cmax (Tmax) Of Navitoclax</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>The amount of time taken to reach Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>AUC of Navitoclax will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time To Cmax (Tmax) Of Ruxolitinib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>The amount of time taken to reach Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib</measure>
    <time_frame>Up To Week 12</time_frame>
    <description>AUC of Ruxolitinib will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Myelofibrosis (MF)</condition>
  <arm_group>
    <arm_group_label>Segment A: ABBV-744 Dose Identification and Optimization</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of ABBV-744 to identify the safe dosing regimen and schedule.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment A: ABBV-744 Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment B: Ruxolitinib + ABBV-744 &quot;Add on&quot; Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as &quot;add-on&quot; therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment C: ABBV-744 + Navitoclax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Segment D: ABBV-744 + Ruxolitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABBV-744</intervention_name>
    <description>Tablet; Oral</description>
    <arm_group_label>Segment A: ABBV-744 Dose Identification and Optimization</arm_group_label>
    <arm_group_label>Segment A: ABBV-744 Monotherapy</arm_group_label>
    <arm_group_label>Segment B: Ruxolitinib + ABBV-744 &quot;Add on&quot; Therapy</arm_group_label>
    <arm_group_label>Segment C: ABBV-744 + Navitoclax</arm_group_label>
    <arm_group_label>Segment D: ABBV-744 + Ruxolitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Navitoclax</intervention_name>
    <description>Tablet; Oral</description>
    <arm_group_label>Segment C: ABBV-744 + Navitoclax</arm_group_label>
    <other_name>ABT-263</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ruxolitinib</intervention_name>
    <description>Tablet; Oral</description>
    <arm_group_label>Segment B: Ruxolitinib + ABBV-744 &quot;Add on&quot; Therapy</arm_group_label>
    <arm_group_label>Segment D: ABBV-744 + Ruxolitinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Laboratory values indicative of adequate bone marrow, renal, and hepatic function&#xD;
             meeting protocol criteria.&#xD;
&#xD;
          -  Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of&#xD;
             the 7 days prior to Day 1 with at least 2 symptoms with a score &gt;=3 or a total score&#xD;
             of &gt;=10.&#xD;
&#xD;
          -  Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF),&#xD;
             post-polycythemia vera MF (PPV-MF) or post-essential thrombocytopenia MF (PET-MF) as&#xD;
             defined by the World Health Organization (WHO).&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of &lt;= 2.&#xD;
&#xD;
          -  Intermediate - 2, or High-Risk disease as defined by the Dynamic International&#xD;
             Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable&#xD;
             splenomegaly &gt;=5 centimeters [cm] below costal margin are also eligible).&#xD;
&#xD;
          -  Splenomegaly defined as spleen palpation measurement &gt;= 5 cm below costal margin or&#xD;
             spleen volume &gt;= 450 cubic cms as assessed by Magnetic Resonance Imaging (MRI) or&#xD;
             Computed Tomography (CT) scan (for Segments A and C, baseline spleen assessment must&#xD;
             be obtained &gt; 7 days after discontinuation of most recent Myelofibrosis (MF) therapy.&#xD;
             If possible, this assessment should occur within 10 days of Cycle 1 Day 1).&#xD;
&#xD;
        Segment-Specific Prior Therapy Criteria:&#xD;
&#xD;
          -  Segment A:&#xD;
&#xD;
               -  Prior exposure to one or more Janus Kinase inhibitors (JAKi),[the most recent of&#xD;
                  which was discontinued &gt; 14 days prior to Cycle 1 Day 1] and are intolerant,&#xD;
                  resistant, refractory or lost response to the JAKi.&#xD;
&#xD;
          -  Segment B:&#xD;
&#xD;
               -  Currently receiving ruxolitinib AND&#xD;
&#xD;
               -  Willingness to reduce ruxolitinib dose (if on a higher dose); and on a stable&#xD;
                  dose for 14 days or longer prior to Cycle 1 Day 1; AND&#xD;
&#xD;
               -  At least one of the following criteria (a, b, or c):&#xD;
&#xD;
                    1. &gt;= 24 weeks duration of current ruxolitinib course, with evidence of disease&#xD;
                       that is resistant, refractory, or has lost response to ruxolitinib therapy;&#xD;
&#xD;
                    2. &lt; 24 weeks duration of current ruxolitinib course with documented&#xD;
                       resistance, refractories, or loss of response, as defined by any of the&#xD;
                       following:&#xD;
&#xD;
                         -  Appearance of new splenomegaly that is palpable to at least 5 cm below&#xD;
                            the left costal margin (LCM), in participants with no evidence of&#xD;
                            splenomegaly prior to the initiation of ruxolitinib.&#xD;
&#xD;
                         -  &gt;=100% increase in the palpable distance below the LCM, in participants&#xD;
                            with measurable spleen distance 5 - 10 cm prior to the initiation of&#xD;
                            ruxolitinib.&#xD;
&#xD;
                         -  &gt;=50% increase in the palpable distance below the LCM, in participants&#xD;
                            with measurable spleen &gt; 10 cm prior to the initiation of ruxolitinib.&#xD;
&#xD;
                         -  A spleen volume increase &gt;= 25% (as assessed by MRI or CT) in&#xD;
                            participants with a spleen volume assessment available prior to the&#xD;
                            initiation of ruxolitinib.&#xD;
&#xD;
                    3. Prior treatment with ruxolitinib for &gt;= 28 days complicated by any of the&#xD;
                       following:&#xD;
&#xD;
                         -  Development of red blood cell transfusion requirement (at least 2&#xD;
                            units/month for 2 months).&#xD;
&#xD;
                         -  Grade &gt;= 3 adverse events of neutropenia and/or anemia while on&#xD;
                            ruxolitinib treatment, with improvement or resolution upon dose&#xD;
                            reduction.&#xD;
&#xD;
          -  Segment C:&#xD;
&#xD;
               -  Prior exposure to one or more JAKi (the most recent of which was discontinued &gt;&#xD;
                  14 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or&#xD;
                  lost response to the JAKi.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Segment-Specific Prior Therapy Criteria:&#xD;
&#xD;
          -  Segment A:&#xD;
&#xD;
               -  Prior exposure to one or more Bromodomain and Extra-Terminal (BET) inhibitors.&#xD;
&#xD;
          -  Segment B:&#xD;
&#xD;
               -  Prior exposure to one or more BET inhibitors.&#xD;
&#xD;
          -  Segment C:&#xD;
&#xD;
               -  Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL)-2&#xD;
                  and/or BCL- XL inhibitor, including navitoclax.&#xD;
&#xD;
          -  Segment D:&#xD;
&#xD;
               -  Prior exposure to JAKi and/or any BET 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_official>
    <last_name>ABBVIE INC.</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>ABBVIE CALL CENTER</last_name>
    <phone>844-663-3742</phone>
    <email>abbvieclinicaltrials@abbvie.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Davis Comprehensive Cancer Center /ID# 221790</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center /ID# 224623</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Roswell Park Comprehensive Cancer Center /ID# 222557</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Mount Sinai Hospital /ID# 221549</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College /ID# 227069</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center Research /ID# 222802</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma, Stephenson Cancer Center /ID# 224095</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104-5418</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science Univ /ID# 221801</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246-2003</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>VA Puget Sound Health Care System /ID# 224208</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98108-1597</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Austral /ID# 228909</name>
      <address>
        <city>Pilar</city>
        <state>Buenos Aires</state>
        <zip>1629</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Italiano de Buenos Aires /ID# 226945</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <state>Ciudad Autonoma De Buenos Aires</state>
        <zip>1199</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Townsville University Hospital /ID# 225859</name>
      <address>
        <city>Douglas</city>
        <state>Queensland</state>
        <zip>4814</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital /ID# 241677</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Perth Hospital /ID# 241678</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas da Universidade Federal de Goiás /ID# 226636</name>
      <address>
        <city>Goiania</city>
        <state>Goias</state>
        <zip>74605-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre /ID# 226635</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein /ID# 226640</name>
      <address>
        <city>São Paulo</city>
        <state>Sao Paulo</state>
        <zip>05652-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 226637</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20231-050</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01323-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 226639</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>SHAT Hematologic Diseases /ID# 226007</name>
      <address>
        <city>Sofia</city>
        <zip>1756</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>UMHAT Sveta Marina /ID# 226681</name>
      <address>
        <city>Varna</city>
        <zip>9010</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Icegclinic /Id# 231086</name>
      <address>
        <city>La Florida</city>
        <state>Region Metropolitana De Santiago</state>
        <zip>8241479</zip>
        <country>Chile</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fundacion Arturo Lopez Perez /ID# 225037</name>
      <address>
        <city>Providencia</city>
        <state>Region Metropolitana Santiago</state>
        <zip>7500921</zip>
        <country>Chile</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sociedad de Investigaciones Médicas Limitada /ID# 224175</name>
      <address>
        <city>Temuco</city>
        <zip>4810469</zip>
        <country>Chile</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249</name>
      <address>
        <city>Gyongyos</city>
        <state>Heves</state>
        <zip>3200</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem /ID# 224085</name>
      <address>
        <city>Budapest</city>
        <zip>1085</zip>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Chaim Sheba Medical Center /ID# 222151</name>
      <address>
        <city>Ramat Gan</city>
        <state>Tel-Aviv</state>
        <zip>5265601</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Center /ID# 223548</name>
      <address>
        <city>Tel Aviv-Yafo</city>
        <state>Tel-Aviv</state>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hadassah Medical Center-Hebrew University /ID# 243852</name>
      <address>
        <city>Jerusalem</city>
        <state>Yerushalayim</state>
        <zip>91120</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397</name>
      <address>
        <city>Milan</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Kyushu University Hospital /ID# 228035</name>
      <address>
        <city>Fukuoka-shi</city>
        <state>Fukuoka</state>
        <zip>812-8582</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hokkaido University Hospital /ID# 228038</name>
      <address>
        <city>Sapporo-shi</city>
        <state>Hokkaido</state>
        <zip>060-8648</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Osaka Metropolitan University Hospital /ID# 225502</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka</state>
        <zip>545-8586</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Yamanashi Hospital /ID# 225503</name>
      <address>
        <city>Chuo-shi</city>
        <state>Yamanashi</state>
        <zip>409-3821</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Inje University Busan Paik Hospital /ID# 233707</name>
      <address>
        <city>Busan</city>
        <zip>47392</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Santa Creu i Sant Pau /ID# 238501</name>
      <address>
        <city>Barcelona</city>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Maranon /ID# 233279</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Orebro Universitetssjukhuset /ID# 228514</name>
      <address>
        <city>Orebro</city>
        <state>Orebro Lan</state>
        <zip>701 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Akademiska Sjukhuset /ID# 228515</name>
      <address>
        <city>Uppsala</city>
        <state>Uppsala Lan</state>
        <zip>751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 234215</name>
      <address>
        <city>Ankara</city>
        <zip>06200</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Koc Universitesi Hastanesi Translasyonel Tip Arastirma Merkezi /ID# 234214</name>
      <address>
        <city>Istanbul</city>
        <zip>34010</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Chile</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>China</country>
    <country>Russian Federation</country>
    <country>Ukraine</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ABBV-744</keyword>
  <keyword>Navitoclax</keyword>
  <keyword>Ruxolitinib</keyword>
  <keyword>ABT-263</keyword>
  <keyword>Cancer</keyword>
  <keyword>Myelofibrosis</keyword>
  <keyword>MF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primary Myelofibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Navitoclax</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04454658
org study id: M20-247
secondary id: 2020-001225-32
nct id: NCT04454658
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body.
      MF disturbs the body's normal production of blood cells, causing extensive scarring in the
      bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The
      purpose of this study is to see how safe and tolerable ABBV-744 is, when given alone, and in
      combination with ruxolitinib or navitoclax, for adult participants with MF.

      ABBV-744 is an investigational drug being developed for the treatment of MF. The study has 4
      segments - A, B, C, and D. In Segment A, the safe dosing regimen of ABBV-744 is identified
      and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of
      ABBV-744 with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis
      of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.

      In Segment A, participants will receive different doses and schedules of oral ABBV-744 tablet
      to identify safe dosing regimen. Additional participants will be enrolled at the identified
      monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and
      ABBV-744 will be given as "add-on" therapy. In Segment C, participants will receive ABBV-744
      and oral navitoclax. In Segment D, participants will receive ABBV-744 and ruxolitinib.
      Participants will receive treatment until disease progression or the participants are not
      able to tolerate the study drugs.

      There may be higher treatment burden for participants in this trial compared to their
      standard of care. Participants will attend regular visits during the study at a hospital or
      clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow
      tests, checking for side effects, and completing questionnaires.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Adverse Events
time frame: Up to Approximately 1 year from start of study
description: An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
measure: Percentage Of Participants Who Achieve Spleen Volume Reduction Of 35% Or Greater (SVR35)
time frame: Up To Week 24
description: Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
measure: Maximum Observed Plasma Concentration (Cmax) of ABBV-744
time frame: Up To Week 12
description: Maximum observed plasma concentration (Cmax) of ABBV-744.
measure: Time To Cmax (Tmax) Of ABBV-744
time frame: Up To Week 12
description: The amount of time taken to reach Cmax.
measure: Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744
time frame: Up To Week 12
description: AUC of ABBV-744 will be calculated.
measure: Half-Life (t1/2) Of ABBV-744
time frame: Up To Week 12
description: Half-life of ABBV-744 will be calculated.
measure: Accumulation Ratio Of ABBV-744
time frame: Up To Week 12
description: Pharmacokinetic parameters will include accumulation ratio of ABBV-744.
measure: Apparent Clearance (CL/F) Of ABBV-744
time frame: Up To Week 12
description: CL/F of ABBV-744 will be calculated.
measure: Apparent Volume Of Distribution (Vd/F) Of ABBV-744
time frame: Up To Week 12
description: Vd/F of ABBV-744 will be calculated.
measure: Percentage Of Participants With >= 50% Reduction In Total Symptom Score (TSS)
time frame: Up to Week 24
description: TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).
measure: Objective Response Rate (ORR)
time frame: Week 24
description: ORR is defined as the sum of rates of partial remission (PR) or better.
measure: Maximum Observed Plasma Concentration (Cmax) Of Navitoclax
time frame: Up To Week 12
description: Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.
measure: Time To Cmax (Tmax) Of Navitoclax
time frame: Up To Week 12
description: The amount of time taken to reach Cmax.
measure: Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax
time frame: Up To Week 12
description: AUC of Navitoclax will be calculated.
measure: Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib
time frame: Up To Week 12
description: Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.
measure: Time To Cmax (Tmax) Of Ruxolitinib
time frame: Up To Week 12
description: The amount of time taken to reach Cmax.
measure: Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib
time frame: Up To Week 12
description: AUC of Ruxolitinib will be calculated.
arm group label: Segment A: ABBV-744 Dose Identification and Optimization
arm group type: Experimental
description: Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of ABBV-744 to identify the safe dosing regimen and schedule.
arm group label: Segment A: ABBV-744 Monotherapy
arm group type: Experimental
description: Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.
arm group label: Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy
arm group type: Experimental
description: Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.
arm group label: Segment C: ABBV-744 + Navitoclax
arm group type: Experimental
description: Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.
arm group label: Segment D: ABBV-744 + Ruxolitinib
arm group type: Experimental
description: Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.
intervention type: Drug
intervention name: ABBV-744
description: Tablet; Oral
arm group label: Segment A: ABBV-744 Dose Identification and Optimization
arm group label: Segment A: ABBV-744 Monotherapy
arm group label: Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy
arm group label: Segment C: ABBV-744 + Navitoclax
arm group label: Segment D: ABBV-744 + Ruxolitinib
intervention type: Drug
intervention name: Navitoclax
description: Tablet; Oral
arm group label: Segment C: ABBV-744 + Navitoclax
other name: ABT-263
intervention type: Drug
intervention name: Ruxolitinib
description: Tablet; Oral
arm group label: Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy
arm group label: Segment D: ABBV-744 + Ruxolitinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE INC.
role: Study Director
affiliation: AbbVie
last name: ABBVIE CALL CENTER
phone: 844-663-3742
email: abbvieclinicaltrials@abbvie.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
country: Argentina
country: Australia
country: Brazil
country: Bulgaria
country: Chile
country: Hungary
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Spain
country: Sweden
country: Turkey
country: United States
country: China
country: Russian Federation
country: Ukraine
responsible party type: Sponsor
mesh term: Primary Myelofibrosis
mesh term: Navitoclax
sharing ipd: No