<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/NCT03306264</url>
  </required_header>
  <id_info>
    <org_study_id>ASTX727-02</org_study_id>
    <nct_id>NCT03306264</nct_id>
  </id_info>
  <brief_title>Study of ASTX727 vs IV Decitabine in MDS, CMML, and AML</brief_title>
  <official_title>A Phase 3, Randomized, Open-Label, Crossover Study of ASTX727 (Cedazuridine and Decitabine Fixed-Dose Combination) Versus IV Decitabine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), and Acute Myeloid Leukemia (AML)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astex Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astex Pharmaceuticals, Inc.</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Multicenter, randomized, open-label, crossover PK study of ASTX727 versus IV decitabine.&#xD;
      Adult subjects who are candidates to receive IV decitabine will be randomized 1:1 to receive&#xD;
      the ASTX727 tablet Daily×5 in Cycle 1 followed by IV decitabine 20 mg/m^2 Daily×5 in Cycle 2,&#xD;
      or the converse order. After completion of PK studies during the first 2 treatment cycles,&#xD;
      subjects will continue to receive treatment with ASTX727 from Cycle 3 onward (in 28-day&#xD;
      cycles) until disease progression, unacceptable toxicity, or the subject discontinues&#xD;
      treatment or withdraws from the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 3 study will establish PK equivalence of ASTX727 to IV decitabine in approximately&#xD;
      118 evaluable subjects. Eligible subjects will receive both study treatments: oral&#xD;
      investigational drug ASTX727, and IV decitabine, as follows: subjects will be randomly&#xD;
      assigned 1:1 to receive ASTX727 or IV decitabine in Cycle 1 and then cross over to the other&#xD;
      therapy in Cycle 2.&#xD;
&#xD;
      In the ASTX727 cycle, subjects will receive the ASTX727 tablet Daily×5. Serial PK&#xD;
      measurements (blood draws) will be done on Days 1, 2, and 5, along with pre-dose PK&#xD;
      assessments on Days 1-5 and an assessment at 3 hours post dose on Day 3. Subjects will be&#xD;
      required to fast from food for 4 hours on days when receiving ASTX727: at least 2 hours&#xD;
      before and 2 hours after dosing.&#xD;
&#xD;
      In the IV decitabine cycle, subjects will receive a 1-hour infusion of IV decitabine 20&#xD;
      mg/m^2 Daily×5. Serial PK measurements will be done on Days 1 and 5, along with pre-dose and&#xD;
      1-hour post-infusion assessments on Day 3.&#xD;
&#xD;
      In Cycles ≥3, subjects will receive the ASTX727 tablet Daily×5 in 28-day cycles. (No PK&#xD;
      assessments will be done from Cycle 3 onward.)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2018</start_date>
  <completion_date type="Actual">March 28, 2023</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Multicenter, randomized, open-label, 2-period, 2-sequence crossover study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total 5-day Area Under the Curve (AUC) exposures of decitabine</measure>
    <time_frame>18 months</time_frame>
    <description>Primary Endpoint</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events (AEs); the severity (intensity) of AEs will be graded according to CTCAE v4.03.</measure>
    <time_frame>18 months</time_frame>
    <description>Safety assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long Interspersed Nucleotide Elements (LINE)-1 demethylation</measure>
    <time_frame>18 months</time_frame>
    <description>Pharmacodynamics assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum plasma concentration (Cmax)</measure>
    <time_frame>2 months</time_frame>
    <description>Secondary pharmacokinetics parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum concentration (Tmax)</measure>
    <time_frame>2 months</time_frame>
    <description>Secondary pharmacokinetics parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination rate constant</measure>
    <time_frame>2 months</time_frame>
    <description>Secondary pharmacokinetics parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent total systemic clearance</measure>
    <time_frame>2 months</time_frame>
    <description>Secondary pharmacokinetics parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent elimination half life</measure>
    <time_frame>2 months</time_frame>
    <description>Secondary pharmacokinetics parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution</measure>
    <time_frame>2 months</time_frame>
    <description>Secondary pharmacokinetics parameter</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MDS/CMML: Number of participants with complete response (CR), marrow CR, partial response; hematologic improvement based on International Working Group (IWG) 2006 MDS response criteria.</measure>
    <time_frame>18 months</time_frame>
    <description>Efficacy analysis - Clinical response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AML: Number of participants with CR, CR with incomplete platelet recovery (CRp) and CR with incomplete blood count recovery (CRi) based on IWG 2003 AML response criteria</measure>
    <time_frame>18 months</time_frame>
    <description>Efficacy analysis - Clinical response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red blood cell (RBC) transfusion independence: defined as no RBC transfusion for 56 consecutive days.</measure>
    <time_frame>18 months</time_frame>
    <description>Efficacy analysis - RBC transfusion independence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet transfusion independence: defined as no platelet transfusion for 8 consecutive weeks.</measure>
    <time_frame>18 months</time_frame>
    <description>Efficacy analysis - Platelet transfusion independence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leukemia-free survival in MDS/CMML participants: number of days from date of randomization to date when bone marrow or peripheral blood blasts reach ≥20%, or death.</measure>
    <time_frame>18 months</time_frame>
    <description>Efficacy analysis - Leukemia-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival: number of days from date subject was randomized to date of death.</measure>
    <time_frame>18 months</time_frame>
    <description>Efficacy analysis - Overall survival</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Myelodysplastic Syndromes</condition>
  <condition>Chronic Myelomonocytic Leukemia</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <arm_group>
    <arm_group_label>ASTX727</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ASTX727 (cedazuridine + decitabine) - Cycle 1 or Cycle 2 (crossover)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV decitabine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dacogen (decitabine for injection) - Cycle 1 or Cycle 2 (crossover)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ASTX727</intervention_name>
    <description>ASTX727 is a tablet for oral administration, containing the fixed-dose combination of 100 mg cedazuridine (a cytidine deaminase inhibitor) and 35 mg decitabine, given by mouth Dailyx5 in 28-day cycles (in Cycle 1 or Cycle 2, then in Cycle 3 and beyond).</description>
    <arm_group_label>ASTX727</arm_group_label>
    <other_name>cedazuridine + decitabine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dacogen</intervention_name>
    <description>Decitabine 20 mg/m^2 one-hour IV infusion Dailyx5 (in one 28-day cycle: either Cycle 1 or Cycle 2).</description>
    <arm_group_label>IV decitabine</arm_group_label>
    <other_name>decitabine for injection</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able to understand and comply with the study procedures, understand the risks involved&#xD;
             in the study, and provide written informed consent before the first study-specific&#xD;
             procedure; specifically able to comply with the PK assessment schedule during the&#xD;
             first 2 treatment cycles.&#xD;
&#xD;
          2. Men or women ≥18 years who are candidates to receive IV decitabine according to FDA or&#xD;
             European Medicines Agency (EMA) approved indications:&#xD;
&#xD;
               1. In North America: Participants with MDS previously treated or untreated with de&#xD;
                  novo or secondary MDS, including all French-American-British subtypes (refractory&#xD;
                  anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess&#xD;
                  blasts, refractory anemia with excess blasts in transformation, and chronic&#xD;
                  myelomonocytic leukemia [CMML]), and subjects with MDS International Prognostic&#xD;
                  Scoring System (IPSS) int-1, -2, or high-risk MDS.&#xD;
&#xD;
               2. In Europe: Participants with de novo or secondary AML, as defined by the World&#xD;
                  Health Organization (WHO) criteria, who are not candidates for standard induction&#xD;
                  chemotherapy.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
&#xD;
          4. Adequate organ function defined as follows:&#xD;
&#xD;
               1. Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate&#xD;
                  transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine&#xD;
                  transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤2.5 × ULN.&#xD;
&#xD;
               2. Renal: serum creatinine ≤1.5 × ULN or calculated creatinine clearance or&#xD;
                  glomerular filtration rate &gt;50 mL/min/1.73 m2 for subjects with creatinine levels&#xD;
                  above institutional normal.&#xD;
&#xD;
          5. No major surgery within 30 days of first study treatment.&#xD;
&#xD;
          6. Life expectancy of at least 3 months.&#xD;
&#xD;
          7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a&#xD;
             negative pregnancy test at screening. Women of non-childbearing potential are those&#xD;
             who have had a hysterectomy or bilateral oophorectomy, or who have completed&#xD;
             menopause, defined as no menses for at least 1 year AND either age ≥65 years or&#xD;
             follicle-stimulating hormone levels in the menopausal range.&#xD;
&#xD;
          8. Subjects and their partners with reproductive potential must agree to use effective&#xD;
             contraceptive measures during the study and for 3 months after the last dose of study&#xD;
             treatment. Effective contraception includes methods such as oral contraceptives or&#xD;
             double-barrier method (eg, use of a condom AND diaphragm, with spermicide).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior treatment with more than 1 cycle of azacitidine or decitabine. Prior cytotoxic&#xD;
             chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC)&#xD;
             counts.&#xD;
&#xD;
          2. Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia,&#xD;
             sepsis, or systemic infection in the 30 days before screening.&#xD;
&#xD;
          3. Treatment with any investigational drug or therapy within 2 weeks of study treatment,&#xD;
             or 5 half-lives, whichever is longer, before the first dose of study treatment, or&#xD;
             ongoing clinically significant adverse events (AEs) from previous treatment.&#xD;
&#xD;
          4. Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose&#xD;
             of study treatment.&#xD;
&#xD;
          5. Concurrent MDS therapies, including lenalidomide, erythropoietin,&#xD;
             cyclosporine/tacrolimus, granulocyte-colony stimulating factor (G-CSF),&#xD;
             granulocyte-macrophage colony-stimulating factor, etc. (Prior treatment with these&#xD;
             agents is permitted, provided that completion is at least 1 week before the first dose&#xD;
             of study treatment.)&#xD;
&#xD;
          6. Poor medical risk because of other conditions such as uncontrolled systemic diseases,&#xD;
             active uncontrolled infections, or comorbidities that may put the patient at risk of&#xD;
             not being able to complete at least 2 cycles of treatment.&#xD;
&#xD;
          7. Known significant mental illness or other condition, such as active alcohol or other&#xD;
             substance abuse or addiction, that in the opinion of the investigator predisposes the&#xD;
             subject to high risk of noncompliance with the protocol.&#xD;
&#xD;
          8. Rapidly progressive or highly proliferative disease (total white blood cell count of&#xD;
             &gt;15 × 10^9/L) or other criteria that render the subject at high risk of requiring&#xD;
             intensive cytotoxic chemotherapy within the next 3 months.&#xD;
&#xD;
          9. Life-threatening illness or severe organ system dysfunction, such as uncontrolled&#xD;
             congestive heart failure or chronic obstructive pulmonary disease, or other reasons&#xD;
             including laboratory abnormalities, which, in the investigator's opinion, could&#xD;
             compromise the subject's safety, interfere with the absorption or metabolism of&#xD;
             ASTX727, or compromise completion of the study or integrity of the study outcomes.&#xD;
&#xD;
         10. Prior malignancy, except for adequately treated basal cell or squamous cell skin&#xD;
             cancer, in situ cervical cancer, prostate cancer or breast cancer under control with&#xD;
             hormone therapy, or other cancer from which the subject has been disease free for at&#xD;
             least 2 years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pinnacle Research Group</name>
      <address>
        <city>Anniston</city>
        <state>Alabama</state>
        <zip>36207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Clinical Research Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85715</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compassionate Cancer Care Research Group</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgetown University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boca Raton Clinical Research</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Quincy Medical Group</name>
      <address>
        <city>Quincy</city>
        <state>Illinois</state>
        <zip>62301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Blood and Marrow Transplantation</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Cancer Care Associates</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Center of Medical Research</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer &amp; Hematology Centers of Western Michigan</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hackensack</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monter Cancer Center</name>
      <address>
        <city>Lake Success</city>
        <state>New York</state>
        <zip>11042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Sciences University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Penn Allegheny Cancer Institute</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charleston Hematology Oncology Associates</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9179</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Utah Cancer Specialists</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84124</zip>
        <country>United States</country>
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  </location>
  <location>
    <facility>
      <name>Kadlec Clinic Hematology and Oncology</name>
      <address>
        <city>Kennewick</city>
        <state>Washington</state>
        <zip>99336</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniklinikum Salzburg</name>
      <address>
        <city>Salzburg</city>
        <zip>05020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital Hietzing</name>
      <address>
        <city>Vienna</city>
        <zip>01130</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Wels-Grieskirchen</name>
      <address>
        <city>Wels</city>
        <zip>4600</zip>
        <country>Austria</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queen Elizabeth II (QEII) Health Sciences Center</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 2Y9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juravinski Hospital &amp; Cancer Center</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 1C3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital - General Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Center - University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Intégré Universitaire de Santé et de Services Sociaux (CIUSSS) de l'Est-de-l'Ile-de-Montréal - Hôpital Maisonneuve Rosemont</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H1T 2M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FN Ostrava</name>
      <address>
        <city>Ostrava</city>
        <state>Poruba</state>
        <zip>708 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Brno</name>
      <address>
        <city>Brno</city>
        <zip>62500</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni Nemocnice Kralovske Vinohrady FNKV</name>
      <address>
        <city>Praha 10</city>
        <state>Česká Republika</state>
        <zip>10034</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de lutte contre le Cancer Leon Berard</name>
      <address>
        <city>Lyon</city>
        <state>Rhone</state>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Emile Muller</name>
      <address>
        <city>Mulhouse</city>
        <zip>68100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Freiburg</name>
      <address>
        <city>Freiburg im Breisgau</city>
        <state>Baden</state>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Philipps-Universität Marburg, Klinik für Innere medizin, Hämatologie, Onkologie und Immunologie</name>
      <address>
        <city>Marburg</city>
        <state>Hesse</state>
        <zip>35033</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNIVERSITTSKLINIKUM Schleswig-Holstein</name>
      <address>
        <city>Lubeck</city>
        <state>Schleswig-Holstein</state>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Staedtisches Klinikum Braunschweig</name>
      <address>
        <city>Braunschweig</city>
        <zip>38114</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oberärztin für Innere Medizin, Hämato-/Onkologie und Palliativmedizin</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40479</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Halle</name>
      <address>
        <city>Halle</city>
        <zip>06120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Leipzig</name>
      <address>
        <city>Leisnig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Debreceni Egyetem Klinikai Kozpont</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Somogy Megyei KAposi Mor Oktato Korhaz</name>
      <address>
        <city>Kaposvár</city>
        <zip>7400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pecs, 1st Department of Internal Medicine</name>
      <address>
        <city>Pecs</city>
        <zip>7400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Szeged</name>
      <address>
        <city>Szeged</city>
        <zip>6725</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo</name>
      <address>
        <city>Alessandria</city>
        <zip>15121</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AOUC Azienda Ospedaliero-Universitaria Careggi</name>
      <address>
        <city>Firenze</city>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS C Granda OM Policlinico</name>
      <address>
        <city>Milan</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Maggiore della Carità Novara</name>
      <address>
        <city>Novara</city>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Eugenio</name>
      <address>
        <city>Rome</city>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ULSS 8 Vicenza - Ospedale San Bortolo di Vicenza</name>
      <address>
        <city>Vicenza</city>
        <zip>36100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias</name>
      <address>
        <city>Oviedo</city>
        <state>Asturias</state>
        <zip>33011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital U. Marqués de Valdecilla</name>
      <address>
        <city>Santander</city>
        <state>Cantabria</state>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital San Pedro de Alcantara</name>
      <address>
        <city>Cáceres</city>
        <zip>10003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de las Nieves</name>
      <address>
        <city>Granada</city>
        <zip>18012</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reynals</name>
      <address>
        <city>L'Hospitalet De Llobregat</city>
        <zip>08909</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria Navarra</name>
      <address>
        <city>Madrid</city>
        <zip>28027</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria Navarra</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari I Politècnic La Fe</name>
      <address>
        <city>València</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford University Hopsitals NHS Trust</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Fundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <disposition_first_submitted>July 29, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>July 29, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 1, 2022</disposition_first_posted>
  <last_update_submitted>August 31, 2023</last_update_submitted>
  <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MDS</keyword>
  <keyword>CMML</keyword>
  <keyword>decitabine</keyword>
  <keyword>Myelodysplastic Syndromes</keyword>
  <keyword>Chronic Myelomonocytic Leukemia</keyword>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>AML</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>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Acute</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Chronic</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</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>Decitabine</mesh_term>
    <mesh_term>Decitabine and cedazuridine drug combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03306264
org study id: ASTX727-02
nct id: NCT03306264
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Multicenter, randomized, open-label, crossover PK study of ASTX727 versus IV decitabine.
      Adult subjects who are candidates to receive IV decitabine will be randomized 1:1 to receive
      the ASTX727 tablet Daily×5 in Cycle 1 followed by IV decitabine 20 mg/m^2 Daily×5 in Cycle 2,
      or the converse order. After completion of PK studies during the first 2 treatment cycles,
      subjects will continue to receive treatment with ASTX727 from Cycle 3 onward (in 28-day
      cycles) until disease progression, unacceptable toxicity, or the subject discontinues
      treatment or withdraws from the study.
This Phase 3 study will establish PK equivalence of ASTX727 to IV decitabine in approximately
      118 evaluable subjects. Eligible subjects will receive both study treatments: oral
      investigational drug ASTX727, and IV decitabine, as follows: subjects will be randomly
      assigned 1:1 to receive ASTX727 or IV decitabine in Cycle 1 and then cross over to the other
      therapy in Cycle 2.

      In the ASTX727 cycle, subjects will receive the ASTX727 tablet Daily×5. Serial PK
      measurements (blood draws) will be done on Days 1, 2, and 5, along with pre-dose PK
      assessments on Days 1-5 and an assessment at 3 hours post dose on Day 3. Subjects will be
      required to fast from food for 4 hours on days when receiving ASTX727: at least 2 hours
      before and 2 hours after dosing.

      In the IV decitabine cycle, subjects will receive a 1-hour infusion of IV decitabine 20
      mg/m^2 Daily×5. Serial PK measurements will be done on Days 1 and 5, along with pre-dose and
      1-hour post-infusion assessments on Day 3.

      In Cycles ≥3, subjects will receive the ASTX727 tablet Daily×5 in 28-day cycles. (No PK
      assessments will be done from Cycle 3 onward.)
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Multicenter, randomized, open-label, 2-period, 2-sequence crossover study
primary purpose: Treatment
masking: None (Open Label)
measure: Total 5-day Area Under the Curve (AUC) exposures of decitabine
time frame: 18 months
description: Primary Endpoint
measure: Number of participants with adverse events (AEs); the severity (intensity) of AEs will be graded according to CTCAE v4.03.
time frame: 18 months
description: Safety assessment
measure: Long Interspersed Nucleotide Elements (LINE)-1 demethylation
time frame: 18 months
description: Pharmacodynamics assessment
measure: Maximum plasma concentration (Cmax)
time frame: 2 months
description: Secondary pharmacokinetics parameter
measure: Time to reach maximum concentration (Tmax)
time frame: 2 months
description: Secondary pharmacokinetics parameter
measure: Elimination rate constant
time frame: 2 months
description: Secondary pharmacokinetics parameter
measure: Apparent total systemic clearance
time frame: 2 months
description: Secondary pharmacokinetics parameter
measure: Apparent elimination half life
time frame: 2 months
description: Secondary pharmacokinetics parameter
measure: Apparent volume of distribution
time frame: 2 months
description: Secondary pharmacokinetics parameter
measure: MDS/CMML: Number of participants with complete response (CR), marrow CR, partial response; hematologic improvement based on International Working Group (IWG) 2006 MDS response criteria.
time frame: 18 months
description: Efficacy analysis - Clinical response
measure: AML: Number of participants with CR, CR with incomplete platelet recovery (CRp) and CR with incomplete blood count recovery (CRi) based on IWG 2003 AML response criteria
time frame: 18 months
description: Efficacy analysis - Clinical response
measure: Red blood cell (RBC) transfusion independence: defined as no RBC transfusion for 56 consecutive days.
time frame: 18 months
description: Efficacy analysis - RBC transfusion independence
measure: Platelet transfusion independence: defined as no platelet transfusion for 8 consecutive weeks.
time frame: 18 months
description: Efficacy analysis - Platelet transfusion independence
measure: Leukemia-free survival in MDS/CMML participants: number of days from date of randomization to date when bone marrow or peripheral blood blasts reach ≥20%, or death.
time frame: 18 months
description: Efficacy analysis - Leukemia-free survival
measure: Overall survival: number of days from date subject was randomized to date of death.
time frame: 18 months
description: Efficacy analysis - Overall survival
arm group label: ASTX727
arm group type: Experimental
description: ASTX727 (cedazuridine + decitabine) - Cycle 1 or Cycle 2 (crossover)
arm group label: IV decitabine
arm group type: Active Comparator
description: Dacogen (decitabine for injection) - Cycle 1 or Cycle 2 (crossover)
intervention type: Drug
intervention name: ASTX727
description: ASTX727 is a tablet for oral administration, containing the fixed-dose combination of 100 mg cedazuridine (a cytidine deaminase inhibitor) and 35 mg decitabine, given by mouth Dailyx5 in 28-day cycles (in Cycle 1 or Cycle 2, then in Cycle 3 and beyond).
arm group label: ASTX727
other name: cedazuridine + decitabine
intervention type: Drug
intervention name: Dacogen
description: Decitabine 20 mg/m^2 one-hour IV infusion Dailyx5 (in one 28-day cycle: either Cycle 1 or Cycle 2).
arm group label: IV decitabine
other name: decitabine for injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Austria
country: Canada
country: Czechia
country: France
country: Germany
country: Hungary
country: Italy
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Preleukemia
mesh term: Leukemia, Myelomonocytic, Acute
mesh term: Leukemia, Myelomonocytic, Chronic
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Decitabine
mesh term: Decitabine and cedazuridine drug combination
sharing ipd: No