<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/NCT02966782</url>
  </required_header>
  <id_info>
    <org_study_id>M15-522</org_study_id>
    <secondary_id>2016-001904-46</secondary_id>
    <nct_id>NCT02966782</nct_id>
  </id_info>
  <brief_title>A Study Evaluating Venetoclax Alone and in Combination With Azacitidine in Participants With Relapsed/Refractory Myelodysplastic Syndromes (MDS)</brief_title>
  <official_title>A Phase 1b Study Evaluating the Safety and Pharmacokinetics of Venetoclax as a Single-Agent and in Combination With Azacitidine in Subjects With Relapsed/Refractory Myelodysplastic Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene; Genentech, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AbbVie</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and&#xD;
      pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in&#xD;
      participants with relapsed/refractory Myelodysplastic Syndromes (MDS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 7, 2017</start_date>
  <completion_date type="Actual">April 5, 2023</completion_date>
  <primary_completion_date type="Actual">April 5, 2023</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUCt for azacitidine</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clearance (CL) for azacitidine</measure>
    <time_frame>Up to 32 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax for azacitidine</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Maximum plasma concentration (Cmax) of azacitidine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax for venetoclax</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Time to Cmax (peak time, Tmax) for venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Phase 2 Dose (RPTD) and dosing schedules of venetoclax as monotherapy and in combination with azacitidine</measure>
    <time_frame>Measured from Day 1 until day 28 per dose level.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC[0 to infinity] for azacitidine</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Area under the plasma concentration-time curve from Time 0 to infinite time.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax for azacitidine</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Time to Cmax (peak time, Tmax) for azacitidine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC [0-24] for venetoclax</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCt for venetoclax</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of venetoclax</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Maximum plasma concentration (Cmax) of venetoclax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Half-life (t[1/2]) for azacitidine</measure>
    <time_frame>Up to 32 days</time_frame>
    <description>Terminal elimination half-life (t[1/2]) for azacitidine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events (AEs)</measure>
    <time_frame>Up to Maximum of 24 months</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Event-Free Survival (EFS)</measure>
    <time_frame>Measured from the date of the first dose of study drug to date of earliest disease progression, death, or initiation of new non-protocol-specified anti-MDS therapy without documented progression, and for up to 5 years after the last subject is enrolled.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Measured from the date of first dose of study drug to the date of death, and for up to 5 years after the last subject is enrolled.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Modified Overall Response (mORR)</measure>
    <time_frame>Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Proportion of participants with a mORR using best outcome will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to next treatment (TTNT)</measure>
    <time_frame>Measured from first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last subject is enrolled.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mORR</measure>
    <time_frame>Measured from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease (PD), and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Defined as the number of days from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier..</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of platelet (PLT) transfusion independence</measure>
    <time_frame>Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Proportion of participants who become platelet transfusion-independent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Transformation acute myeloid leukemia (AML)</measure>
    <time_frame>Measured from the date of first dose of study drug to the date of documented AML transformation for an anticipated maximum duration of 24 months.</time_frame>
    <description>Defined as blast count greater than or equal to 20% in either peripheral blood or bone marrow.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>Measured from the date of the first dose of study drug to the date of earliest disease progression or death, and for an anticipated maximum duration of 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>ORR (equals the sum of rates of complete remission [CR] + marrow complete remission (mCR) + partial remission [PR]) of venetoclax as a single-agent and in combination with azacitidine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Remission (CR) Rate</measure>
    <time_frame>Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Proportion of subjects who achieved a complete remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of red blood cell (RBC) transfusion independence</measure>
    <time_frame>Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Proportion of red blood cell (RBC) transfusion independence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Complete Response (CR)</measure>
    <time_frame>Measured from date of first response (CR) to the to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Duration of CR will be defined as the number of days from the date of first response CR to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Hematologic Improvement (HI)</measure>
    <time_frame>Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Proportion of participants with HI (erythroid/platelet/neutrophil responses)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of marrow complete remission (mCR)</measure>
    <time_frame>Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Proportion of participants with marrow complete remission with or without hematological improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ORR</measure>
    <time_frame>Measured from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.</time_frame>
    <description>Duration of response (ORR) will be defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Myelodysplastic Syndromes (MDS)</condition>
  <arm_group>
    <arm_group_label>Venetoclax monotherapy (Cohort 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Venetoclax + azacitidine (Cohort 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Safety Expansion (Cohort 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>venetoclax</intervention_name>
    <description>Tablet</description>
    <arm_group_label>Safety Expansion (Cohort 3)</arm_group_label>
    <arm_group_label>Venetoclax + azacitidine (Cohort 2)</arm_group_label>
    <arm_group_label>Venetoclax monotherapy (Cohort 1)</arm_group_label>
    <other_name>ABT-199</other_name>
    <other_name>GDC-0199</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>azacitidine</intervention_name>
    <description>Powder for injection, subcutaneously or intravenous</description>
    <arm_group_label>Safety Expansion (Cohort 3)</arm_group_label>
    <arm_group_label>Venetoclax + azacitidine (Cohort 2)</arm_group_label>
    <other_name>Vidaza</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who have relapsed or refractory MDS.&#xD;
&#xD;
          -  Subject enrolled in venetoclax monotherapy must have documented failure of prior&#xD;
             therapy with a hypomethylating agent (HMA). HMA-failure is defined as:&#xD;
&#xD;
               1. Relapse after initial complete or partial response or hematological improvement&#xD;
                  after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within&#xD;
                  the last 5 years, OR&#xD;
&#xD;
               2. Failure to achieve complete or partial response or hematological improvement&#xD;
                  after at least 4 cycles of azacitidine or at least 4 cycles of decitabine within&#xD;
                  the last 5 years&#xD;
&#xD;
          -  Subjects must have presence of &lt; 20% bone marrow blasts per bone marrow&#xD;
             biopsy/aspirate at screening.&#xD;
&#xD;
          -  Subject is not a candidate to undergo allogenic hematopoietic stem cell&#xD;
             transplantation (HSCT).&#xD;
&#xD;
          -  Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of&#xD;
             ≤2.&#xD;
&#xD;
          -  Subject must have adequate hematologic, renal, and hepatic function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has received prior therapy with a BH3 mimetic.&#xD;
&#xD;
          -  Subject has MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).&#xD;
&#xD;
          -  Subject has MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic&#xD;
             myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable&#xD;
             MDS/MPN.&#xD;
&#xD;
          -  Subject has received allogeneic HSCT or solid organ transplantation.&#xD;
&#xD;
          -  Subject has received a live attenuated vaccine within 4 weeks prior to the first dose&#xD;
             of study drug.&#xD;
&#xD;
          -  Subject is pregnant or breastfeeding.&#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>
  <location>
    <facility>
      <name>University of Arizona Cancer Center - North Campus /ID# 157503</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719-1478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital /ID# 155365</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University /ID# 162544</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duplicate_University of Chicago /ID# 155364</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pediatric Endocrine Associates /ID# 171227</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute /ID# 155361</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts - Worcester /ID# 155366</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia Univ Medical Center /ID# 156388</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-3725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University /ID# 155360</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center /ID# 155362</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St George Hospital /ID# 156037</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital /ID# 155952</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Melbourne /ID# 155950</name>
      <address>
        <city>Fitzroy Melbourne</city>
        <state>Victoria</state>
        <zip>3065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Melbourne Hospital /ID# 155949</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Perth Hospital /ID# 155951</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Mannheim /ID# 156038</name>
      <address>
        <city>Mannheim</city>
        <state>Baden-Wuerttemberg</state>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marien Hospital Duesseldorf /ID# 155518</name>
      <address>
        <city>Duesseldorf</city>
        <state>Nordrhein-Westfalen</state>
        <zip>40479</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Duesseldorf /ID# 154899</name>
      <address>
        <city>Düsseldorf</city>
        <state>Nordrhein-Westfalen</state>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Koeln /ID# 155519</name>
      <address>
        <city>Köln</city>
        <state>Nordrhein-Westfalen</state>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Leipzig /ID# 154897</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 154898</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Halle (Saale) /ID# 158643</name>
      <address>
        <city>Halle (Saale)</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 154896</name>
      <address>
        <city>Munich</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 15, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsed/refractory</keyword>
  <keyword>Venetoclax</keyword>
  <keyword>Azacitidine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Venetoclax</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/NCT02966782
org study id: M15-522
secondary id: 2016-001904-46
nct id: NCT02966782
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and
      pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in
      participants with relapsed/refractory Myelodysplastic Syndromes (MDS).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUCt for azacitidine
time frame: Up to 32 days
description: Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine
measure: Clearance (CL) for azacitidine
time frame: Up to 32 days
measure: Cmax for azacitidine
time frame: Up to 32 days
description: Maximum plasma concentration (Cmax) of azacitidine
measure: Tmax for venetoclax
time frame: Up to 32 days
description: Time to Cmax (peak time, Tmax) for venetoclax
measure: Recommended Phase 2 Dose (RPTD) and dosing schedules of venetoclax as monotherapy and in combination with azacitidine
time frame: Measured from Day 1 until day 28 per dose level.
measure: AUC[0 to infinity] for azacitidine
time frame: Up to 32 days
description: Area under the plasma concentration-time curve from Time 0 to infinite time.
measure: Tmax for azacitidine
time frame: Up to 32 days
description: Time to Cmax (peak time, Tmax) for azacitidine
measure: AUC [0-24] for venetoclax
time frame: Up to 32 days
description: AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax
measure: AUCt for venetoclax
time frame: Up to 32 days
description: Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax
measure: Cmax of venetoclax
time frame: Up to 32 days
description: Maximum plasma concentration (Cmax) of venetoclax
measure: Half-life (t[1/2]) for azacitidine
time frame: Up to 32 days
description: Terminal elimination half-life (t[1/2]) for azacitidine
measure: Number of Participants With Adverse Events (AEs)
time frame: Up to Maximum of 24 months
description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
measure: Event-Free Survival (EFS)
time frame: Measured from the date of the first dose of study drug to date of earliest disease progression, death, or initiation of new non-protocol-specified anti-MDS therapy without documented progression, and for up to 5 years after the last subject is enrolled.
measure: Overall Survival (OS)
time frame: Measured from the date of first dose of study drug to the date of death, and for up to 5 years after the last subject is enrolled.
measure: Rate of Modified Overall Response (mORR)
time frame: Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: Proportion of participants with a mORR using best outcome will be calculated.
measure: Time to next treatment (TTNT)
time frame: Measured from first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last subject is enrolled.
measure: Duration of mORR
time frame: Measured from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease (PD), and for an anticipated maximum duration of 24 months.
description: Defined as the number of days from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier..
measure: Rate of platelet (PLT) transfusion independence
time frame: Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: Proportion of participants who become platelet transfusion-independent
measure: Time to Transformation acute myeloid leukemia (AML)
time frame: Measured from the date of first dose of study drug to the date of documented AML transformation for an anticipated maximum duration of 24 months.
description: Defined as blast count greater than or equal to 20% in either peripheral blood or bone marrow.
measure: Progression-Free Survival (PFS)
time frame: Measured from the date of the first dose of study drug to the date of earliest disease progression or death, and for an anticipated maximum duration of 24 months.
measure: Overall Response Rate (ORR)
time frame: Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: ORR (equals the sum of rates of complete remission [CR] + marrow complete remission (mCR) + partial remission [PR]) of venetoclax as a single-agent and in combination with azacitidine.
measure: Complete Remission (CR) Rate
time frame: Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: Proportion of subjects who achieved a complete remission.
measure: Rate of red blood cell (RBC) transfusion independence
time frame: Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: Proportion of red blood cell (RBC) transfusion independence.
measure: Duration of Complete Response (CR)
time frame: Measured from date of first response (CR) to the to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.
description: Duration of CR will be defined as the number of days from the date of first response CR to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
measure: Rate of Hematologic Improvement (HI)
time frame: Measured from Cycle 1 Day 1 as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: Proportion of participants with HI (erythroid/platelet/neutrophil responses)
measure: Rate of marrow complete remission (mCR)
time frame: Measured from Cycle 1 Day 1 (C1D1) as long as the subject continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months.
description: Proportion of participants with marrow complete remission with or without hematological improvement.
measure: Duration of ORR
time frame: Measured from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months.
description: Duration of response (ORR) will be defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.
arm group label: Venetoclax monotherapy (Cohort 1)
arm group type: Experimental
arm group label: Venetoclax + azacitidine (Cohort 2)
arm group type: Experimental
arm group label: Safety Expansion (Cohort 3)
arm group type: Experimental
intervention type: Drug
intervention name: venetoclax
description: Tablet
arm group label: Safety Expansion (Cohort 3)
arm group label: Venetoclax + azacitidine (Cohort 2)
arm group label: Venetoclax monotherapy (Cohort 1)
other name: ABT-199
other name: GDC-0199
intervention type: Drug
intervention name: azacitidine
description: Powder for injection, subcutaneously or intravenous
arm group label: Safety Expansion (Cohort 3)
arm group label: Venetoclax + azacitidine (Cohort 2)
other name: Vidaza
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE INC.
role: Study Director
affiliation: AbbVie
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country: Australia
country: Germany
country: United States
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Azacitidine
mesh term: Venetoclax
sharing ipd: No