<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/NCT03248479</url>
  </required_header>
  <id_info>
    <org_study_id>5F9005</org_study_id>
    <secondary_id>2017-000678-12</secondary_id>
    <nct_id>NCT03248479</nct_id>
  </id_info>
  <brief_title>Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Participants With Hematological Malignancies</brief_title>
  <official_title>A Phase 1b Trial of Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gilead Sciences</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>
      The primary objectives of this study are:&#xD;
&#xD;
        -  To confirm the safety and tolerability of magrolimab monotherapy in a&#xD;
           relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome&#xD;
           (MDS) population, and of magrolimab in combination with azacitidine in previously&#xD;
           untreated participants with AML or MDS and participants with R/R AML and MDS&#xD;
&#xD;
        -  To evaluate the efficacy of magrolimab monotherapy in R/R AML/MDS, and of magrolimab in&#xD;
           combination with azacitidine in previously untreated participants with AML/MDS, or R/R&#xD;
           AML/MDS as measured by complete remission (CR) rate for participants with AML and&#xD;
           higher-risk MDS, and duration of complete response for participants with AML and&#xD;
           higher-risk MDS, and duration of CR for participants with AML and higher-risk MDS&#xD;
&#xD;
        -  To evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or&#xD;
           combination with azacitidine in low-risk MDS participants as measured by red blood cell&#xD;
           (RBC) transfusion independence rate&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 8, 2017</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</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>Percentage of Participant Experiencing Adverse Events</measure>
    <time_frame>First dose date up to 4 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Remission (CR) Rate For Participants With AML</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>The CR rate is the proportion of participants who achieved CR, as defined by the Investigator based on European Leukemia Net (ELN) AML recommendations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>RBC Transfusion Independence Rate for Participants with Low-Risk MDS</measure>
    <time_frame>Up to 8 weeks</time_frame>
    <description>RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 8 week consecutive period at any time after starting therapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Remission Rate for Participants with MDS</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>The CR rate is the proportion of MDS participants who reach morphologic CR while on study per International Working Group (IWG) 2006 criteria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of Complete Remission (DCR) in Participants with AML and MDS</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>For AML participants: The DCR will be measured from the time measurement criteria are first met for CR (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR) until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented.&#xD;
For MDS participants: The DCR will be measured from the time measurement criteria are first met for CR until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration for Magrolimab</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>R/R and TN/U Cohorts: Pre-magrolimab infusion: Cycle 1 Days 1, 8, 15 &amp; 22, Cycle 2 Days 1 &amp; 8, every other cycle beginning with Cycle 3-Cycle 13 Day 1, End of Treatment (EOT) (after last dose of magrolimab or within 7 days of EOT decision), Safety Follow up Visit (SFU) (30 days after last dose of magrolimab); 1 hour (± 15 minutes) post magrolimab infusion: Cycle 1 Days 1 &amp; 8, Cycle 2 Day 1, every other cycle Cycle 3-Cycle 13 Day 1&#xD;
RBC MDS Cohort: Pre-magrolimab infusion: Cycle 1 Days 1, 8 &amp; 15, Cycle 2 Days 1 &amp; 15, every other cycle Day 1 beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1; EOT; SFU; 15 minutes (± 15 minutes) post magrolimab infusion: Cycle 2 Day 1&#xD;
Cycle length is 28 days&#xD;
Infusion Duration: 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants who Developed Anti-Magrolimab Antibodies</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>R/R, TN/U Expansion, R/R MDS Cohorts: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, Cycle 3-13 every 2 cycles Day 1, EOT (after last dose or within 7 days of EOT decision), SFU (30 days after last dose of magrolimab)&#xD;
RBC MDS Cohort: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1, EOT, &amp; SFU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AML Participants With Objective Response Based on ELN AML Recommendations</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AML Participants With Objective Response Based on IWG AML Response Criteria</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) in MDS as Defined by IWG 2006 MDS Response Criteria</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The ORR is the proportion of patients who reach CR (including morphologic CR, CRMRD-, cCR, and mCR), CRi, CRh, PR, marrow CR, or MLFS while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) for Participants with AML</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The duration of response will be measured from the time measurement criteria are met for complete remission (CR) (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR), incomplete blood count recovery (CRi), partial hematologic recovery (CRh), partial remission (PR), marrow CR, or morphologic leukemia-free state (MLFS), whichever is first recorded, until the first date that recurrent or progressive disease, or death within 8 weeks of the last response assessment with evidence of no disease magrolimab progression is objectively documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response for Participants with MDS</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The DOR will be measured from the time measurement criteria are first met for objective response as assessed by IWG MDS criteria until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RBC Transfusion Independence (no RBC transfusions for at least an 8-week consecutive period)</measure>
    <time_frame>Up to 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-week RBC Transfusion Independence Rates</measure>
    <time_frame>Up to 12 Weeks</time_frame>
    <description>RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 12 week consecutive period at any time after starting therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Hemoglobin Increase on Therapy</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) for Participants with AML or MDS</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of PFS is defined as the time from the date of study treatment initiation until the date of documented disease progression or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse Free Survival (RFS) for Participants with AML or MDS</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of RFS is defined from the first date of attaining a CR (including morphologic CR, CRMRD-, cCR, and mCR) until the date of AML relapse or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event Free Survival (EFS) for Participants with AML or MDS</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of EFS is defined as the time from the date of study treatment initiation until the date of documented disease progression, death from any cause, or treatment failure (defined as permanent treatment discontinuation from any cause), whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) for Participants with AML or MDS</measure>
    <time_frame>Up to 6 years</time_frame>
    <description>The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of minimal residual disease (MRD) Negativity Using a Multiparameter Flow Cytometry-Based Assay for Participants on Treatment</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Remission with Partial Hematologic Recovery (CRh)</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">258</enrollment>
  <condition>Hematological Malignancies</condition>
  <arm_group>
    <arm_group_label>R/R Safety Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1 Week 1 (Day 1 and 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11 and 15; and 30 mg/kg weekly thereafter starting Cycle 3 up to end of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>R/R Expansion Cohort:</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1 Week 1 (Day 1 and Day 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11 and 15; 30 mg/kg weekly on Cycle 1 Day 22 through end of Cycle 2, then 30 mg/kg every 2 weeks starting Cycle 3 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>R/R MDS Magrolimab Monotherapy Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Day 11, 15, 22, weekly on Cycle 2, and then biweekly starting Cycle 3 up to end of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment-naive Unfit (TNU) Dose Evaluation Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Day 11, 15, 22, and then weekly starting Cycle 2 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment-naive Unfit (TNU) Dose Expansion Cohort</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1; 15 mg/kg weekly for Cycle 1 Day 8; 30 mg/kg weekly through end of cycle 2; and then 30 mg/kg every 2 weeks starting Cycle 3 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RBC transfusion-dependent low-risk MDS, Safety Run-in Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab on Cycle 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15, and 22; and 60 mg/kg every 4 weeks starting on Cycle 2 Day 1 and thereafter up to end of the study. For participants who do not respond after Cycle 2, azacitidine 75 mg/m^2 may be added on subsequent cycles (ie starting at Cycle 3) on Days 1 to 5 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RBC transfusion-dependent low-risk MDS, Expansion Phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 mg/kg magrolimab on Cycle 1 Day 1; at 30 mg/kg on Cycle 1 Days 8, 15, and 22; and 60 mg/kg every 4 starting on Cycle 2 Day 1 and thereafter up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 5 of each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rollover</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants on a previous AML Phase 1 trial (SCI-CD47-002; NCT02678338) with clinical benefit on magrolimab treatment will receive the same dose level (0.1 mg/kg up to 30.0mg/kg based on the cohort to which the participant was assigned) twice weekly or may transition to once weekly dosing at the discretion of the Investigator and approval from Gilead.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Magrolimab</intervention_name>
    <description>Administered intravenously</description>
    <arm_group_label>R/R Expansion Cohort:</arm_group_label>
    <arm_group_label>R/R MDS Magrolimab Monotherapy Cohort</arm_group_label>
    <arm_group_label>R/R Safety Cohort</arm_group_label>
    <arm_group_label>RBC transfusion-dependent low-risk MDS, Expansion Phase</arm_group_label>
    <arm_group_label>RBC transfusion-dependent low-risk MDS, Safety Run-in Phase</arm_group_label>
    <arm_group_label>Rollover</arm_group_label>
    <arm_group_label>Treatment-naive Unfit (TNU) Dose Evaluation Cohort</arm_group_label>
    <arm_group_label>Treatment-naive Unfit (TNU) Dose Expansion Cohort</arm_group_label>
    <other_name>Hu5F9-G4</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Azacitidine</intervention_name>
    <description>Administered according to region-specific drug labeling either subcutaneously or intravenously</description>
    <arm_group_label>R/R Expansion Cohort:</arm_group_label>
    <arm_group_label>RBC transfusion-dependent low-risk MDS, Expansion Phase</arm_group_label>
    <arm_group_label>RBC transfusion-dependent low-risk MDS, Safety Run-in Phase</arm_group_label>
    <arm_group_label>Treatment-naive Unfit (TNU) Dose Evaluation Cohort</arm_group_label>
    <arm_group_label>Treatment-naive Unfit (TNU) Dose Expansion Cohort</arm_group_label>
    <other_name>VIDAZA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Meets the criteria below for the appropriate cohort:&#xD;
&#xD;
               1. Relapsed/Refractory Cohorts: Pathologically confirmed relapsed or refractory&#xD;
                  (primary refractory and/or relapsed refractory) AML or confirmed intermediate,&#xD;
                  high, or very high risk MDS that is relapsed, refractory or intolerant to&#xD;
                  conventional therapy&#xD;
&#xD;
               2. Treatment-naive/ Unfit Cohorts: Previously untreated individuals with&#xD;
                  histological confirmation of AML who are ineligible for treatment with a standard&#xD;
                  cytarabine and anthracycline induction regimen; or previously untreated&#xD;
                  individuals with intermediate, high, or very high risk MDS. Prior and concurrent&#xD;
                  therapy with hydroxyurea, oral etoposide, erythroid and/or myeloid growth factors&#xD;
                  is allowed.&#xD;
&#xD;
               3. Rollover Cohort: Individuals on active magrolimab therapy on the Phase 1 AML&#xD;
                  (SCI-CD47-002; NCT02678338) trial who are deriving clinical benefit by&#xD;
                  Investigator assessment&#xD;
&#xD;
               4. RBC transfusion dependent low risk MDS cohort: Transfusion-dependent MDS&#xD;
                  individuals who are very low or low risk by IPSS-R with previous treatment with&#xD;
                  an erythroid stimulating agent or lenalidomide.&#xD;
&#xD;
          -  White blood cell (WBC) count ≤ 20 x 10^3/mcL&#xD;
&#xD;
          -  Adequate performance status and hematological, liver, and kidney function&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with CD47 or signal regulatory protein alpha (SIRPα) targeting agents&#xD;
             (with exception of magrolimab for individuals in the Rollover cohort).&#xD;
&#xD;
          -  Treatment-naive/Unfit Cohorts Only: Any prior anti-leukemic therapy (excluding&#xD;
             hydroxyurea or oral etoposide), prior treatment with hypomethylating agents and/or low&#xD;
             dose cytarabine.&#xD;
&#xD;
          -  Acute promyelocytic leukemia.&#xD;
&#xD;
          -  Known inherited or acquired bleeding disorders.&#xD;
&#xD;
          -  Previous allogeneic hematopoietic stem cell transplant within 6 months prior to&#xD;
             enrollment, active graft versus host disease (GVHD), or requiring transplant-related&#xD;
             immunosuppression.&#xD;
&#xD;
          -  Clinical suspicion of active central nervous system (CNS) involvement by leukemia&#xD;
&#xD;
          -  Known active or chronic hepatitis B or C infection or HIV&#xD;
&#xD;
          -  Pregnancy or active breastfeeding&#xD;
&#xD;
        Note: Other protocol defined Inclusion/Exclusion criteria may apply.&#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>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope National Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego (UCSD)</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Clinical and Translational Research Center (CTRC)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chao Family Comprehensive Cancer Center - UC Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Of Miami - Miller School Of Medicine, Sylvester Comprehensive Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center &amp; Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</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/ Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid America Division, Inc.</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College - New York-Presbyterian Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennesssee Oncology - Centennial Clinic Location</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Charles A. Simmons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas 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>Medical College of WI Froedtert Hospital</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford Centre for Respiratory Medicine Churchill Hospital, Oxford University Hospitals NHS Trust</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.gileadclinicaltrials.com/study/?id=5F9005</url>
    <description>Gilead Clinical Trials Website</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>June 16, 2023</last_update_submitted>
  <last_update_submitted_qc>June 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>CD47</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Magrolimab</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/NCT03248479
org study id: 5F9005
secondary id: 2017-000678-12
nct id: NCT03248479
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objectives of this study are:

        -  To confirm the safety and tolerability of magrolimab monotherapy in a
           relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome
           (MDS) population, and of magrolimab in combination with azacitidine in previously
           untreated participants with AML or MDS and participants with R/R AML and MDS

        -  To evaluate the efficacy of magrolimab monotherapy in R/R AML/MDS, and of magrolimab in
           combination with azacitidine in previously untreated participants with AML/MDS, or R/R
           AML/MDS as measured by complete remission (CR) rate for participants with AML and
           higher-risk MDS, and duration of complete response for participants with AML and
           higher-risk MDS, and duration of CR for participants with AML and higher-risk MDS

        -  To evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or
           combination with azacitidine in low-risk MDS participants as measured by red blood cell
           (RBC) transfusion independence rate
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participant Experiencing Adverse Events
time frame: First dose date up to 4 years
measure: Complete Remission (CR) Rate For Participants With AML
time frame: Up to 4 years
description: The CR rate is the proportion of participants who achieved CR, as defined by the Investigator based on European Leukemia Net (ELN) AML recommendations.
measure: RBC Transfusion Independence Rate for Participants with Low-Risk MDS
time frame: Up to 8 weeks
description: RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 8 week consecutive period at any time after starting therapy.
measure: Complete Remission Rate for Participants with MDS
time frame: Up to 4 years
description: The CR rate is the proportion of MDS participants who reach morphologic CR while on study per International Working Group (IWG) 2006 criteria
measure: Duration of Complete Remission (DCR) in Participants with AML and MDS
time frame: Up to 4 years
description: For AML participants: The DCR will be measured from the time measurement criteria are first met for CR (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR) until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented.
For MDS participants: The DCR will be measured from the time measurement criteria are first met for CR until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented
measure: Serum Concentration for Magrolimab
time frame: Up to 6 years
description: R/R and TN/U Cohorts: Pre-magrolimab infusion: Cycle 1 Days 1, 8, 15 & 22, Cycle 2 Days 1 & 8, every other cycle beginning with Cycle 3-Cycle 13 Day 1, End of Treatment (EOT) (after last dose of magrolimab or within 7 days of EOT decision), Safety Follow up Visit (SFU) (30 days after last dose of magrolimab); 1 hour (± 15 minutes) post magrolimab infusion: Cycle 1 Days 1 & 8, Cycle 2 Day 1, every other cycle Cycle 3-Cycle 13 Day 1
RBC MDS Cohort: Pre-magrolimab infusion: Cycle 1 Days 1, 8 & 15, Cycle 2 Days 1 & 15, every other cycle Day 1 beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1; EOT; SFU; 15 minutes (± 15 minutes) post magrolimab infusion: Cycle 2 Day 1
Cycle length is 28 days
Infusion Duration: 3 hours (± 30 minutes) for 1mg/kg; 2 hours for 15 mg/kg, 30 mg/kg and 60 mg/kg
measure: Percentage of Participants who Developed Anti-Magrolimab Antibodies
time frame: Up to 6 years
description: R/R, TN/U Expansion, R/R MDS Cohorts: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, Cycle 3-13 every 2 cycles Day 1, EOT (after last dose or within 7 days of EOT decision), SFU (30 days after last dose of magrolimab)
RBC MDS Cohort: Before study drug (magrolimab or azacitidine), within 72 hours for initial dose and within 24 hours for subsequent doses Cycle 1 Days 1 and 8, Cycle 2 Day 1, beginning with Cycle 3 through Cycle 7 and then every third cycle through Cycle 13 Day 1, EOT, & SFU
measure: Percentage of AML Participants With Objective Response Based on ELN AML Recommendations
time frame: Up to 6 years
measure: Percentage of AML Participants With Objective Response Based on IWG AML Response Criteria
time frame: Up to 6 years
measure: Objective Response Rate (ORR) in MDS as Defined by IWG 2006 MDS Response Criteria
time frame: Up to 6 years
description: The ORR is the proportion of patients who reach CR (including morphologic CR, CRMRD-, cCR, and mCR), CRi, CRh, PR, marrow CR, or MLFS while on study.
measure: Duration of Response (DOR) for Participants with AML
time frame: Up to 6 years
description: The duration of response will be measured from the time measurement criteria are met for complete remission (CR) (including morphologic CR, complete remission without minimal residual disease (CRMRD-), cytogenetic complete remission (cCR), and molecular complete remission (mCR), incomplete blood count recovery (CRi), partial hematologic recovery (CRh), partial remission (PR), marrow CR, or morphologic leukemia-free state (MLFS), whichever is first recorded, until the first date that recurrent or progressive disease, or death within 8 weeks of the last response assessment with evidence of no disease magrolimab progression is objectively documented.
measure: Duration of Response for Participants with MDS
time frame: Up to 6 years
description: The DOR will be measured from the time measurement criteria are first met for objective response as assessed by IWG MDS criteria until the first date that recurrent disease or death within 8 weeks of the last response assessment with evidence of no disease recurrence is objectively documented.
measure: RBC Transfusion Independence (no RBC transfusions for at least an 8-week consecutive period)
time frame: Up to 8 weeks
measure: 12-week RBC Transfusion Independence Rates
time frame: Up to 12 Weeks
description: RBC transfusion independence rate is defined by the lack of RBC transfusions for at least an 12 week consecutive period at any time after starting therapy.
measure: Mean Hemoglobin Increase on Therapy
time frame: Up to 6 years
measure: Progression Free Survival (PFS) for Participants with AML or MDS
time frame: Up to 6 years
description: The length of PFS is defined as the time from the date of study treatment initiation until the date of documented disease progression or death from any cause, whichever occurs first.
measure: Relapse Free Survival (RFS) for Participants with AML or MDS
time frame: Up to 6 years
description: The length of RFS is defined from the first date of attaining a CR (including morphologic CR, CRMRD-, cCR, and mCR) until the date of AML relapse or death from any cause, whichever occurs first.
measure: Event Free Survival (EFS) for Participants with AML or MDS
time frame: Up to 6 years
description: The length of EFS is defined as the time from the date of study treatment initiation until the date of documented disease progression, death from any cause, or treatment failure (defined as permanent treatment discontinuation from any cause), whichever occurs first.
measure: Overall Survival (OS) for Participants with AML or MDS
time frame: Up to 6 years
description: The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.
measure: Level of minimal residual disease (MRD) Negativity Using a Multiparameter Flow Cytometry-Based Assay for Participants on Treatment
time frame: Up to 6 years
measure: Complete Remission with Partial Hematologic Recovery (CRh)
time frame: Up to 6 years
arm group label: R/R Safety Cohort
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1 Week 1 (Day 1 and 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11 and 15; and 30 mg/kg weekly thereafter starting Cycle 3 up to end of the study.
arm group label: R/R Expansion Cohort:
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1 Week 1 (Day 1 and Day 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Days 11 and 15; 30 mg/kg weekly on Cycle 1 Day 22 through end of Cycle 2, then 30 mg/kg every 2 weeks starting Cycle 3 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.
arm group label: R/R MDS Magrolimab Monotherapy Cohort
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Day 11, 15, 22, weekly on Cycle 2, and then biweekly starting Cycle 3 up to end of the study.
arm group label: Treatment-naive Unfit (TNU) Dose Evaluation Cohort
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab on Cycle 1 (Days 1, 4); 15 mg/kg on Cycle 1 Day 8; 30 mg/kg on Cycle 1 Day 11, 15, 22, and then weekly starting Cycle 2 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.
arm group label: Treatment-naive Unfit (TNU) Dose Expansion Cohort
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab twice weekly for Cycle 1; 15 mg/kg weekly for Cycle 1 Day 8; 30 mg/kg weekly through end of cycle 2; and then 30 mg/kg every 2 weeks starting Cycle 3 up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 7 of each cycle.
arm group label: RBC transfusion-dependent low-risk MDS, Safety Run-in Phase
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab on Cycle 1 Day 1; 30 mg/kg on Cycle 1 Days 8, 15, and 22; and 60 mg/kg every 4 weeks starting on Cycle 2 Day 1 and thereafter up to end of the study. For participants who do not respond after Cycle 2, azacitidine 75 mg/m^2 may be added on subsequent cycles (ie starting at Cycle 3) on Days 1 to 5 of each cycle.
arm group label: RBC transfusion-dependent low-risk MDS, Expansion Phase
arm group type: Experimental
description: Participants will receive 1 mg/kg magrolimab on Cycle 1 Day 1; at 30 mg/kg on Cycle 1 Days 8, 15, and 22; and 60 mg/kg every 4 starting on Cycle 2 Day 1 and thereafter up to end of the study + azacitidine 75 mg/m^2 on Days 1 to 5 of each cycle.
arm group label: Rollover
arm group type: Experimental
description: Participants on a previous AML Phase 1 trial (SCI-CD47-002; NCT02678338) with clinical benefit on magrolimab treatment will receive the same dose level (0.1 mg/kg up to 30.0mg/kg based on the cohort to which the participant was assigned) twice weekly or may transition to once weekly dosing at the discretion of the Investigator and approval from Gilead.
intervention type: Drug
intervention name: Magrolimab
description: Administered intravenously
arm group label: R/R Expansion Cohort:
arm group label: R/R MDS Magrolimab Monotherapy Cohort
arm group label: R/R Safety Cohort
arm group label: RBC transfusion-dependent low-risk MDS, Expansion Phase
arm group label: RBC transfusion-dependent low-risk MDS, Safety Run-in Phase
arm group label: Rollover
arm group label: Treatment-naive Unfit (TNU) Dose Evaluation Cohort
arm group label: Treatment-naive Unfit (TNU) Dose Expansion Cohort
other name: Hu5F9-G4
intervention type: Drug
intervention name: Azacitidine
description: Administered according to region-specific drug labeling either subcutaneously or intravenously
arm group label: R/R Expansion Cohort:
arm group label: RBC transfusion-dependent low-risk MDS, Expansion Phase
arm group label: RBC transfusion-dependent low-risk MDS, Safety Run-in Phase
arm group label: Treatment-naive Unfit (TNU) Dose Evaluation Cohort
arm group label: Treatment-naive Unfit (TNU) Dose Expansion Cohort
other name: VIDAZA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
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country: United Kingdom
country: United States
url: https://www.gileadclinicaltrials.com/study/?id=5F9005
description: Gilead Clinical Trials Website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Hematologic Neoplasms
mesh term: Azacitidine
mesh term: Magrolimab
sharing ipd: No