<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/NCT04402723</url>
  </required_header>
  <id_info>
    <org_study_id>ZGDAML1</org_study_id>
    <nct_id>NCT04402723</nct_id>
  </id_info>
  <brief_title>Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML</brief_title>
  <official_title>A Dose-escalated Phase Ⅰ Trial to Assess the Tolerance and Pharmacokinetics of Combination of Donafenib and Cytarabine/Daunorubicin in Relapsed AML Patient</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Suzhou Zelgen Biopharmaceuticals Co.,Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase Ⅰ study of Donafenib, an oral multikinase inhibitor that targets Raf kinase and&#xD;
      receptor tyrosine kinases, is to assess safety and pharmacokinetics in patients with Relapsed&#xD;
      AML.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Donafenib is a multikinase inhibitor which is acting on various cellular pathways involved in&#xD;
      the genesis of acute myeloid leukemia (AML). Donafenib is therefore a promising candidate for&#xD;
      improvement of chemotherapy results in AML. This clinical trial evaluates the safety and&#xD;
      pharmacokinetics of Donafenib combination with Cytarabine/Daunorubicin for AML in patients&#xD;
      between 18 and 55 years of age.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Corporate policy adjustments&#xD;
  </why_stopped>
  <start_date type="Actual">November 6, 2018</start_date>
  <completion_date type="Actual">February 9, 2022</completion_date>
  <primary_completion_date type="Actual">February 9, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety(including the type, severity and frequency of AE)</measure>
    <time_frame>through study completion, an average of 2 months</time_frame>
    <description>Safety of combination of donafenib with Cytarabine/Daunorubicin in relapsed AML patients.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Acute Myeloid Leukemia (AML)</condition>
  <arm_group>
    <arm_group_label>Donafenib, 0.2g</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donafenib,0.2g,bid,Combination with Cytarabine and Daunorubicin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Donafenib,0.3g</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Donafenib,0.3g,bid,Combination with Cytarabine and Daunorubicin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Donafenib</intervention_name>
    <description>In first 28-days-cycle, eligible subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination with Daunorubicin 60mg/m2/d, for first 3 days, and Cytarabine 100mg/m2/d, for first 7 days. If CR or CRi is observed, subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination Cytarabine 2g/m2/q12h, for first 3 days, in next 28-day-cycle.</description>
    <arm_group_label>Donafenib, 0.2g</arm_group_label>
    <arm_group_label>Donafenib,0.3g</arm_group_label>
    <other_name>Cytarabine and Daunorubicin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with diagnosed AML (except APL) according to the FAB and WHO classification,&#xD;
             including AML evolving from MDS or other hematologic diseases and AML after previous&#xD;
             cytotoxic therapy or radiation (secondary AML) .&#xD;
&#xD;
          -  Patients with diagnosed Relapsed AML according to Chinese Guidelines for the Diagnosis&#xD;
             and Treatment of Acute Myeloid Leukemia.&#xD;
&#xD;
          -  relapse after 6 months of an morphological remission.&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 55 years.&#xD;
&#xD;
          -  BMI ≥ 18 and ≤27.&#xD;
&#xD;
          -  Informed consent, personally signed and dated to participate in the study.&#xD;
&#xD;
          -  ECOG performance status of 0-1.&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks.&#xD;
&#xD;
          -  Total serum bilirubin ≤1.5×ULN.&#xD;
&#xD;
          -  Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5×ULN.&#xD;
&#xD;
          -  Serum creatinine ≤1.5×ULN.&#xD;
&#xD;
          -  glomerular filtration rate ≥60 mL/min, as calculated with the Cockcroft-Gault formula.&#xD;
&#xD;
          -  alkaline phosphatase ≤1.5×ULN.&#xD;
&#xD;
          -  urine protein ≤1+, or Urine protein was quantified for 24h ≤0.5g.&#xD;
&#xD;
          -  INR/PTT &lt;1.5×ULN.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are not eligible for standard chemotherapy as per discretion of the&#xD;
             treating physician.&#xD;
&#xD;
          -  Patients who have been treated with bone marrow transplantation.&#xD;
&#xD;
          -  Central nervous system manifestation of AML.&#xD;
&#xD;
          -  Cardiac disease: heart failure NYHA III or IV; unstable coronary artery disease (MI&#xD;
             more than 6 months prior to study entry is permitted); serious cardiac ventricular&#xD;
             arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are&#xD;
             permitted).&#xD;
&#xD;
          -  Patients who have thrombosis events within 6 months prior to study entry is permitted.&#xD;
&#xD;
          -  Pregnancy or breastfeed.&#xD;
&#xD;
          -  Chronic pulmonary disease with relevant hypoxia.&#xD;
&#xD;
          -  Patients undergoing dialysis.&#xD;
&#xD;
          -  Known HIV and/or hepatitis C infection.&#xD;
&#xD;
          -  Evidence or history of severe non-leukemia associated bleeding diathesis or&#xD;
             coagulopathy.&#xD;
&#xD;
          -  Evidence or recent history of CNS disease, including primary or metastatic brain&#xD;
             tumors, seizure disorders.&#xD;
&#xD;
          -  Blood pressure (BP) higher than systolic 140 mmHg and/or diastolic 90 mmHg after best&#xD;
             treatment.&#xD;
&#xD;
          -  Any severe concomitant condition which makes it undesirable for the patient to&#xD;
             participate in the study or which could jeopardize compliance of the protocol.&#xD;
&#xD;
          -  Patients with major surgery, open biopsy or significant traumatic injury within 4&#xD;
             weeks prior to study entry is permitted.&#xD;
&#xD;
          -  Serious, non-healing wound, ulcer or bone fracture.&#xD;
&#xD;
          -  Infection need antibiotic treatment.&#xD;
&#xD;
          -  Cumulative therapeutic dose of Daunorubicin more than 300mg/m2.&#xD;
&#xD;
          -  Concurrent malignancies other than AML.&#xD;
&#xD;
          -  History of organ allograft.&#xD;
&#xD;
          -  Allergy to study medication or excipients in study medication.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianxiang Wang, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Hematology and Blood Disease Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Hematology and Blood Disease Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>May 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2022</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, Myeloid, Acute</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>Daunorubicin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04402723
org study id: ZGDAML1
nct id: NCT04402723
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This phase Ⅰ study of Donafenib, an oral multikinase inhibitor that targets Raf kinase and
      receptor tyrosine kinases, is to assess safety and pharmacokinetics in patients with Relapsed
      AML.
Donafenib is a multikinase inhibitor which is acting on various cellular pathways involved in
      the genesis of acute myeloid leukemia (AML). Donafenib is therefore a promising candidate for
      improvement of chemotherapy results in AML. This clinical trial evaluates the safety and
      pharmacokinetics of Donafenib combination with Cytarabine/Daunorubicin for AML in patients
      between 18 and 55 years of age.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety(including the type, severity and frequency of AE)
time frame: through study completion, an average of 2 months
description: Safety of combination of donafenib with Cytarabine/Daunorubicin in relapsed AML patients.
arm group label: Donafenib, 0.2g
arm group type: Experimental
description: Donafenib,0.2g,bid,Combination with Cytarabine and Daunorubicin.
arm group label: Donafenib,0.3g
arm group type: Experimental
description: Donafenib,0.3g,bid,Combination with Cytarabine and Daunorubicin
intervention type: Drug
intervention name: Donafenib
description: In first 28-days-cycle, eligible subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination with Daunorubicin 60mg/m2/d, for first 3 days, and Cytarabine 100mg/m2/d, for first 7 days. If CR or CRi is observed, subjects will be given Donafenib 0.2/0.3g, bid, for first 14 days, combination Cytarabine 2g/m2/q12h, for first 3 days, in next 28-day-cycle.
arm group label: Donafenib, 0.2g
arm group label: Donafenib,0.3g
other name: Cytarabine and Daunorubicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Jianxiang Wang, Doctor
role: Principal Investigator
affiliation: Institute of Hematology and Blood Disease Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Leukemia, Myeloid, Acute
mesh term: Cytarabine
mesh term: Daunorubicin