<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/NCT03030612</url>
  </required_header>
  <id_info>
    <org_study_id>CR108756</org_study_id>
    <secondary_id>2016-002151-17</secondary_id>
    <secondary_id>ARGX-110-1601</secondary_id>
    <nct_id>NCT03030612</nct_id>
  </id_info>
  <brief_title>A Study of ARGX-110 in Combination With Azacytidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)</brief_title>
  <official_title>A Phase I/II, Open-label, Dose-Escalating Study With a Proof of Concept Cohort to Evaluate the Safety, Tolerability and Efficacy of ARGX-110 in Combination With Azacytidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia (AML) or High Risk Myelodysplatic Syndrome (MDS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OncoVerity, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>argenx</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>OncoVerity, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the maximum tolerated dose (MTD) of ARGX-110 and/or&#xD;
      the recommended Phase II dose (RP2D) in combination with a standard dose of azacytidine (AZA)&#xD;
      in Phase 1; and to evaluate efficacy of ARGX-110 when administered at a RP2D level&#xD;
      established in Phase I in combination with a standard dose of AZA (proof-of concept) by&#xD;
      evaluating overall response rate (ORR) in Phase 2.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">August 2022</completion_date>
  <primary_completion_date type="Actual">August 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Number of Participants with Dose Limiting Toxicity (DLT)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>DLTs will be defined as any of the following drug-related events: Any grade 3 or higher drug related non-hematological toxicity or; Grade 3 or higher IRRs or; inability to administer the next dose due to a drug-related adverse event or a delay of the administration of the next dose due to toxicities for more than 14 days despite adequate medication or; drug-related grade 4 febrile neutropenia or; drug-related grade 4 anemia which cannot be adequately treated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Overall Response Rate (ORR)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>ORR is defined as the sum of Complete remission (CR), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) at the ARGX-110 RP2D level that was established in Phase 1 according to established response criteria for Acute myeloid leukemia (AML).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with Adverse Events</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Cmax is the maximum observed concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Trough Concentration (Ctrough) of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Ctrough is defined as the observed serum concentration before dosing or at the end of the dosing interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve from Time Zero to Infinite (AUC[0-infinity]) of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>AUC(0-infinity) is defined as area under the serum analyte concentration-time curve from time 0 to infinite time of ARGX-110.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCtau)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>AUCtau is the area under the serum concentration-time curve during the dosing interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Apparent Volume of Distribution (Vd/F) of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Total Systemic Clearance (CL) of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>CL is the total systemic clearance of drug after intravenous (IV) administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Elimination Half-Life (t1/2) of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>t1/2 is defined as the time measured for the serum concentration to decrease by 1 half of its original concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with Minimal Residual Disease (MRD) to ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Minimal residual disease assessments will be performed on bone marrow aspirates and/or whole blood by flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with Anti-drug Antibodies (ADA) to ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Venous blood samples and bone marrow aspirate will be used to evaluate presence of anti-drug antibodies to ARGX-110. Participants with titer of confirmed positive samples for ARGX-110 antibodies will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with Complete Remission (CR)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Complete remission is defined as number of participants who have bone marrow blasts less than (&lt;) 5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (&gt;) 1.0 * 10^9 per liter (L) (1000 per microliter [µL]); platelet count &gt; 100 * 10^9/L (100.000/mc); independence of red cell transfusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with CR with Incomplete Recovery (CRi)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>CRi is defined as number of participants who have all CR criteria except for residual neutropenia (&lt; 1.0 * 10^9/L [1000/mc]) or thrombocytopenia (&lt; 100 * 10^9/L [100.000/mc]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with Morphologic Leukemia-free State (MLFS)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>MLFS is defined as number of participants who have bone marrow blasts &lt; 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with Partial remission (PR)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>PR is defined as number of participants who have all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Time to Response</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Time to response is defined as response measured from the time from first dose of study drug to date of response (CR, CRi, MLFS, PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Duration of Response</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Duration of response is defined as the date of achievement of a response (CR, CRi, MLFS, PR) until the date of relapse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Relapse-Free Survival (RFS)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>RFS is defined as disease relapse or participant death from any cause; measured from the date of achievement of a remission (CR, CRi) until the date of relapse or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Overall Survival (OS)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>OS is defined as death from any cause; measured from the date of first dose to the date of death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants with 30 Day and 60 Day Mortality</measure>
    <time_frame>30 and/or 60 days after the first administration</time_frame>
    <description>Number of participants with 30 Day and 60 Day Mortality will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Number of Participants Achieving Transfusion Independence (TI)</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Number of participants reaching greater than or equal to (&gt;=) 8 consecutive weeks without red blood cell (RBC-TI) and/or platelet (PLT-TI) transfusion. The first day of the &gt;=8-week period with no transfusions is noted as the time at which participants first achieved TI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Time to Transfusion Independence</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Time until TI for RBC and/or PLT will be measured from the date of entry into a study to the first day of the 8-weeks period with no transfusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Duration of Transfusion Independence</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Time between the last transfusion before the start of the TI period and the first transfusion after the start of the TI period, which occurred &gt;=8 weeks later.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Time to Neutrophil Recovery</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Time to neutrophil recovery will be calculated from number of days from Day 1 of commencing study treatment to first day neutrophils 0.5 * 10^9 per liter or 1.0 * 10^9 per liter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1 and Phase 2: Time to Platelet Recovery</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Time to platelet recovery will be calculated from number of days from day 1 of commencing study treatment to first day neutrophils 50 * 10^9 per liter or 100 * 10^9 per liter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker Assessment of ARGX-110</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Biomarkers including CD70 and CD27 assessment will be performed on bone marrow aspirates and/or whole blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Levels of T, B and NK Cells</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Levels of T, B and NK cells will be reported by immunophenotyping (performed by flow cytometry or mass cytometry). .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Levels of B Cells</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Levels of B cells will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Levels of NK Cells</measure>
    <time_frame>Up to 3.6 years</time_frame>
    <description>Levels of NK cells will be reported.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Leukemia, Myeloid, Acute</condition>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>ARGX-110 with Azacytidine (AZA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m^2 BSA, administered SC/IV as per local practice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARGX-110</intervention_name>
    <description>ARGX-110 will be administered intravenously.</description>
    <arm_group_label>ARGX-110 with Azacytidine (AZA)</arm_group_label>
    <other_name>Cusatuzumab</other_name>
    <other_name>JNJ-74494550</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZA</intervention_name>
    <description>AZA will be administered subcutaneously/intravenously.</description>
    <arm_group_label>ARGX-110 with Azacytidine (AZA)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent form (ICF) indicating an understanding of the purposes, risks,&#xD;
             and procedures required for the study and willingness and ability to participate in&#xD;
             the study&#xD;
&#xD;
          -  Acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) (according to&#xD;
             2016 World Health Organization [WHO] classification definition of greater than or&#xD;
             equal to [&gt;=] 20 percent [%] blasts) (bone marrow) unsuitable for intensive treatment&#xD;
             (including stem cell transplantation) with a curative intent, but eligible to receive&#xD;
             azacytidine (AZA) treatment&#xD;
&#xD;
          -  Expected life expectancy &gt;= 3 months, at the discretion of the investigator&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2&#xD;
&#xD;
          -  Women of childbearing potential having a negative serum pregnancy test at screening&#xD;
             and within 48 hours before infusion of ARGX-110 on Day -14, and willing to use an&#xD;
             effective contraceptive method (intrauterine devices, hormonal contraceptives,&#xD;
             contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions&#xD;
             with prolonged release) during the study and for at least 3 months after the last&#xD;
             study drug administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior or concurrent malignancy, except for the following: (1) adequately treated basal&#xD;
             cell or squamous cell skin cancer; (2) carcinoma in situ of the cervix; (3) carcinoma&#xD;
             in situ of the breast; (4) incidental histological finding of Prostate cancer (Tumour,&#xD;
             Node, Metastasis [TNM] stage T1a or T1b), or; (5) Any other cancer from which the&#xD;
             subject has been disease-free for more than 2 years&#xD;
&#xD;
          -  Any previous AML or MDS chemo- or radiotherapy (with the exception of&#xD;
             hydroxyurea/Litalir for leukocyte control which should be discontinued by the first&#xD;
             day of AZA, local radiation therapy, therapy for basal or squamous cell carcinoma of&#xD;
             the skin)&#xD;
&#xD;
          -  Treatment with any investigational product within 4 weeks before the first&#xD;
             administration of ARGX-110&#xD;
&#xD;
          -  Any known active or chronic infection, including human immunodeficiency virus (HIV)&#xD;
             and hepatitis B or C virus infection&#xD;
&#xD;
          -  Any other concurrent disease or medical condition that is likely to interfere with&#xD;
             study procedures or results, or that in the opinion of the investigator would&#xD;
             constitute a hazard for participating in this study&#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>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Marseille Cedex 9</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paris Cedex 10</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pierre - Bénite Cedex</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toulouse Cedex 9</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Aarau</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bern</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zürich</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Switzerland</country>
  </location_countries>
  <removed_countries>
    <country>Italy</country>
  </removed_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 23, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03030612
org study id: CR108756
secondary id: 2016-002151-17
secondary id: ARGX-110-1601
nct id: NCT03030612
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated device: No
The purpose of this study is to determine the maximum tolerated dose (MTD) of ARGX-110 and/or
      the recommended Phase II dose (RP2D) in combination with a standard dose of azacytidine (AZA)
      in Phase 1; and to evaluate efficacy of ARGX-110 when administered at a RP2D level
      established in Phase I in combination with a standard dose of AZA (proof-of concept) by
      evaluating overall response rate (ORR) in Phase 2.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Number of Participants with Dose Limiting Toxicity (DLT)
time frame: Up to 3.6 years
description: DLTs will be defined as any of the following drug-related events: Any grade 3 or higher drug related non-hematological toxicity or; Grade 3 or higher IRRs or; inability to administer the next dose due to a drug-related adverse event or a delay of the administration of the next dose due to toxicities for more than 14 days despite adequate medication or; drug-related grade 4 febrile neutropenia or; drug-related grade 4 anemia which cannot be adequately treated.
measure: Phase 2: Overall Response Rate (ORR)
time frame: Up to 3.6 years
description: ORR is defined as the sum of Complete remission (CR), CR with incomplete recovery (CRi), morphologic leukemia-free state (MLFS), partial remission (PR) at the ARGX-110 RP2D level that was established in Phase 1 according to established response criteria for Acute myeloid leukemia (AML).
measure: Phase 1 and Phase 2: Number of Participants with Adverse Events
time frame: Up to 3.6 years
description: An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
measure: Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of ARGX-110
time frame: Up to 3.6 years
description: Cmax is the maximum observed concentration.
measure: Phase 1 and Phase 2: Trough Concentration (Ctrough) of ARGX-110
time frame: Up to 3.6 years
description: Ctrough is defined as the observed serum concentration before dosing or at the end of the dosing interval.
measure: Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve from Time Zero to Infinite (AUC[0-infinity]) of ARGX-110
time frame: Up to 3.6 years
description: AUC(0-infinity) is defined as area under the serum analyte concentration-time curve from time 0 to infinite time of ARGX-110.
measure: Phase 1 and Phase 2: Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCtau)
time frame: Up to 3.6 years
description: AUCtau is the area under the serum concentration-time curve during the dosing interval.
measure: Phase 1 and Phase 2: Apparent Volume of Distribution (Vd/F) of ARGX-110
time frame: Up to 3.6 years
description: Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].
measure: Phase 1 and Phase 2: Total Systemic Clearance (CL) of ARGX-110
time frame: Up to 3.6 years
description: CL is the total systemic clearance of drug after intravenous (IV) administration.
measure: Phase 1 and Phase 2: Elimination Half-Life (t1/2) of ARGX-110
time frame: Up to 3.6 years
description: t1/2 is defined as the time measured for the serum concentration to decrease by 1 half of its original concentration.
measure: Phase 1 and Phase 2: Number of Participants with Minimal Residual Disease (MRD) to ARGX-110
time frame: Up to 3.6 years
description: Minimal residual disease assessments will be performed on bone marrow aspirates and/or whole blood by flow cytometry.
measure: Phase 1 and Phase 2: Number of Participants with Anti-drug Antibodies (ADA) to ARGX-110
time frame: Up to 3.6 years
description: Venous blood samples and bone marrow aspirate will be used to evaluate presence of anti-drug antibodies to ARGX-110. Participants with titer of confirmed positive samples for ARGX-110 antibodies will be reported.
measure: Phase 1 and Phase 2: Number of Participants with Complete Remission (CR)
time frame: Up to 3.6 years
description: Complete remission is defined as number of participants who have bone marrow blasts less than (<) 5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>) 1.0 * 10^9 per liter (L) (1000 per microliter [µL]); platelet count > 100 * 10^9/L (100.000/mc); independence of red cell transfusions.
measure: Phase 1 and Phase 2: Number of Participants with CR with Incomplete Recovery (CRi)
time frame: Up to 3.6 years
description: CRi is defined as number of participants who have all CR criteria except for residual neutropenia (< 1.0 * 10^9/L [1000/mc]) or thrombocytopenia (< 100 * 10^9/L [100.000/mc]).
measure: Phase 1 and Phase 2: Number of Participants with Morphologic Leukemia-free State (MLFS)
time frame: Up to 3.6 years
description: MLFS is defined as number of participants who have bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required.
measure: Phase 1 and Phase 2: Number of Participants with Partial remission (PR)
time frame: Up to 3.6 years
description: PR is defined as number of participants who have all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
measure: Phase 1 and Phase 2: Time to Response
time frame: Up to 3.6 years
description: Time to response is defined as response measured from the time from first dose of study drug to date of response (CR, CRi, MLFS, PR).
measure: Phase 1 and Phase 2: Duration of Response
time frame: Up to 3.6 years
description: Duration of response is defined as the date of achievement of a response (CR, CRi, MLFS, PR) until the date of relapse.
measure: Phase 1 and Phase 2: Relapse-Free Survival (RFS)
time frame: Up to 3.6 years
description: RFS is defined as disease relapse or participant death from any cause; measured from the date of achievement of a remission (CR, CRi) until the date of relapse or death from any cause.
measure: Phase 1 and Phase 2: Overall Survival (OS)
time frame: Up to 3.6 years
description: OS is defined as death from any cause; measured from the date of first dose to the date of death from any cause.
measure: Phase 1 and Phase 2: Number of Participants with 30 Day and 60 Day Mortality
time frame: 30 and/or 60 days after the first administration
description: Number of participants with 30 Day and 60 Day Mortality will be reported.
measure: Phase 1 and Phase 2: Number of Participants Achieving Transfusion Independence (TI)
time frame: Up to 3.6 years
description: Number of participants reaching greater than or equal to (>=) 8 consecutive weeks without red blood cell (RBC-TI) and/or platelet (PLT-TI) transfusion. The first day of the >=8-week period with no transfusions is noted as the time at which participants first achieved TI.
measure: Phase 1 and Phase 2: Time to Transfusion Independence
time frame: Up to 3.6 years
description: Time until TI for RBC and/or PLT will be measured from the date of entry into a study to the first day of the 8-weeks period with no transfusions.
measure: Phase 1 and Phase 2: Duration of Transfusion Independence
time frame: Up to 3.6 years
description: Time between the last transfusion before the start of the TI period and the first transfusion after the start of the TI period, which occurred >=8 weeks later.
measure: Phase 1 and Phase 2: Time to Neutrophil Recovery
time frame: Up to 3.6 years
description: Time to neutrophil recovery will be calculated from number of days from Day 1 of commencing study treatment to first day neutrophils 0.5 * 10^9 per liter or 1.0 * 10^9 per liter.
measure: Phase 1 and Phase 2: Time to Platelet Recovery
time frame: Up to 3.6 years
description: Time to platelet recovery will be calculated from number of days from day 1 of commencing study treatment to first day neutrophils 50 * 10^9 per liter or 100 * 10^9 per liter.
measure: Biomarker Assessment of ARGX-110
time frame: Up to 3.6 years
description: Biomarkers including CD70 and CD27 assessment will be performed on bone marrow aspirates and/or whole blood.
measure: Phase 1: Levels of T, B and NK Cells
time frame: Up to 3.6 years
description: Levels of T, B and NK cells will be reported by immunophenotyping (performed by flow cytometry or mass cytometry). .
measure: Phase 1: Levels of B Cells
time frame: Up to 3.6 years
description: Levels of B cells will be reported.
measure: Phase 1: Levels of NK Cells
time frame: Up to 3.6 years
description: Levels of NK cells will be reported.
arm group label: ARGX-110 with Azacytidine (AZA)
arm group type: Experimental
description: Phase 1: Participants will receive loading dose of ARGX-110 1 milligram per kilogram (mg/kg) body weight (cohort 1), 3 mg/kg body weight (cohort 2), 10 mg/kg body weight (cohort 3) or 20 mg/kg body weight (cohort 4) administered intravenously (IV) in combination with AZA standard dose of 75 milligram per meter square (mg/m^2) body surface area (BSA) administered subcutaneously (SC) / intravenously (IV). Phase 2: Participants will receive loading dose of ARGX-110 IV at a recommended dose for Phase 2 (RP2D) level from phase 1 in combination with AZA standard dose of 75 mg/m^2 BSA, administered SC/IV as per local practice.
intervention type: Drug
intervention name: ARGX-110
description: ARGX-110 will be administered intravenously.
arm group label: ARGX-110 with Azacytidine (AZA)
other name: Cusatuzumab
other name: JNJ-74494550
intervention type: Drug
intervention name: AZA
description: AZA will be administered subcutaneously/intravenously.
arm group label: ARGX-110 with Azacytidine (AZA)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
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country: France
country: Switzerland
country: Italy
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
sharing ipd: Undecided