<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/NCT02193958</url>
  </required_header>
  <id_info>
    <org_study_id>FF1050101US01</org_study_id>
    <nct_id>NCT02193958</nct_id>
  </id_info>
  <brief_title>Study of FF-10501-01 in Patients With Relapsed or Refractory Hematological Malignancies</brief_title>
  <official_title>A Phase 1/2a, Dose Escalation Study of FF-10501-01 for the Treatment of Advanced Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fujifilm Pharmaceuticals U.S.A., Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fujifilm Pharmaceuticals U.S.A., Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase 1/2a Dose Escalation Study of FF-10501-01 in Patients with Relapsed or Refractory&#xD;
      Hematological Malignancies to determine the safety and tolerability. A total of 6 cohorts&#xD;
      will be enrolled in Phase 1 to establish the MTD. A total of 20 subjects with MDS/CMML&#xD;
      treated at the RP2D are planned, including MDS/CMML subjects treated at the RP2D in Phase 1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will receive FF-10501-01 orally on a twice daily schedule for 14, 21 or 28 days&#xD;
      repeated every 28 days (=1 cycle). Disease assessments, including analysis of blood and bone&#xD;
      marrow aspirates, will be performed at the end of Cycle 1 and every 2 cycles thereafter.&#xD;
      Subjects who demonstrate objective response or stable disease will be allowed to continue&#xD;
      therapy with FF-10501-01 until progression of disease, observation of unacceptable adverse&#xD;
      events, intercurrent illness or changes in condition that prevent further study&#xD;
      participation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">October 15, 2019</completion_date>
  <primary_completion_date type="Actual">August 9, 2019</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>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety assessed by adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicity (DLT), dose reductions, delays or withdrawals due to toxicity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determination of overall response rates.</measure>
    <time_frame>Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.</time_frame>
    <description>Response criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the pharmacokinetic profile of FF-10501-01 and its metabolite.</measure>
    <time_frame>Evaluated at three timepoints: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1. Each cycle is 28 days in length.</time_frame>
    <description>Cmax, Tmax, Half-life, AUC, Clearance, Volume of Distribution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in xanthosine monophosphate (XMP) as a pharmacodynamic marker.</measure>
    <time_frame>Evaluated at three timepoints: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1. Each cycle is 28 days in length.</time_frame>
    <description>Xanthosine monophosphate (XMP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate the proportion of subjects who achieve hematologic improvement in peripheral blood or bone marrow blast count.</measure>
    <time_frame>Responses and survival assessed at the end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.</time_frame>
    <description>Response Criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate progression-free survival (PFS).</measure>
    <time_frame>Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.</time_frame>
    <description>Response Criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate overall survival (OS).</measure>
    <time_frame>Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.</time_frame>
    <description>Response criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>AML</condition>
  <condition>CMML</condition>
  <condition>MDS</condition>
  <arm_group>
    <arm_group_label>Phase 1: Lowest dose of FF-10501-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FF-10501-01 tablets BID every 14 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1: 2x lowest dose of FF-10501-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1: 4x lowest dose of FF-10501-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1: 6x lowest dose of FF-10501-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1: 8x lowest dose of FF-10101-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>8x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ph 2a: FF-10501-01 at 8x in MDS/CMML</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FF-10501-01 tablets BID every 21 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ph1:8x lowest dose FF10101-01 for 21 day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FF-10501-01 tablets BID every 21 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ph1: 8x lowest dose FF-10101-01 28 day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FF-10501-01 tablets BID every 28 days of a 28 day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ph1: 10X lowest dose FF-10501-01 14 day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF-10501-01</intervention_name>
    <description>FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.</description>
    <arm_group_label>Ph 2a: FF-10501-01 at 8x in MDS/CMML</arm_group_label>
    <arm_group_label>Ph1: 10X lowest dose FF-10501-01 14 day</arm_group_label>
    <arm_group_label>Ph1: 8x lowest dose FF-10101-01 28 day</arm_group_label>
    <arm_group_label>Ph1:8x lowest dose FF10101-01 for 21 day</arm_group_label>
    <arm_group_label>Phase 1: 2x lowest dose of FF-10501-01</arm_group_label>
    <arm_group_label>Phase 1: 4x lowest dose of FF-10501-01</arm_group_label>
    <arm_group_label>Phase 1: 6x lowest dose of FF-10501-01</arm_group_label>
    <arm_group_label>Phase 1: 8x lowest dose of FF-10101-01</arm_group_label>
    <arm_group_label>Phase 1: Lowest dose of FF-10501-01</arm_group_label>
    <other_name>Single Group Assignment</other_name>
    <other_name>Drug FF-10501-01</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed advanced hematologic malignancies;&#xD;
&#xD;
        Phase 1:&#xD;
&#xD;
          -  High-risk MDS/CMML (defined as ≥ 10% peripheral blood or marrow blasts and/or IPSS&#xD;
             score ≥ 1.5) and relapsed or refractory to prior therapy&#xD;
&#xD;
          -  AML relapsed or refractory to prior therapy, or ≥ 60 years of age and not a candidate&#xD;
             for other therapies&#xD;
&#xD;
        Phase 2a:&#xD;
&#xD;
          -  MDS/CMML, relapsed from, or refractory to, prior HMA therapy; the latter defined as&#xD;
             failure to achieve clinical remission (CR), partial remission (PR) or hematologic&#xD;
             improvement (HI) after previous HMA therapy (≥ 4 cycles of azacitidine or decitabine),&#xD;
             or progression during, or toxicity to previous HMA therapy precluding further HMA&#xD;
             treatment, and,&#xD;
&#xD;
          -  Bone marrow blast count ≥ 10% or peripheral blast count ≥ 5%, or IPSS-R score ≥ 3.5.&#xD;
&#xD;
               -  At least 3 weeks beyond the last chemotherapy, targeted anticancer agent, major&#xD;
                  surgery or experimental treatment and recovered from all acute toxicities (≤&#xD;
                  Grade 1). Hydroxyurea used to control peripheral blast counts is permitted up to&#xD;
                  Day 7 of treatment on study.&#xD;
&#xD;
               -  Adequate performance status: ECOG ≤ 2;&#xD;
&#xD;
               -  Adequate renal and hepatic function:&#xD;
&#xD;
          -  creatinine ≤ 2.0 mg/dL, or calculated creatinine clearance ≥ 45 mL/min&#xD;
&#xD;
          -  total bilirubin ≤ 2 times the upper limit of normal (ULN)&#xD;
&#xD;
          -  ALT/AST ≤ 2 times ULN&#xD;
&#xD;
               -  Negative serum pregnancy test&#xD;
&#xD;
               -  Ability to provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known history of coronary artery disease, angina, myocardial infarction, congestive&#xD;
             heart failure, cardiac arrhythmia or any other type of heart disease present within&#xD;
             the last 6 months&#xD;
&#xD;
          -  Known family history of hereditary heart disease&#xD;
&#xD;
          -  QT interval corrected for rate (QTc) &gt; 450 msec on the electrocardiogram (ECG)&#xD;
             obtained at Screening&#xD;
&#xD;
          -  Concomitant medication(s) that may cause QTc prolongation or induce Torsades de&#xD;
             Pointes, with the exception of anti-microbials that are used as standard of care to&#xD;
             prevent or treat infections and other such drugs that are considered by the&#xD;
             Investigator to be essential for the care of the patient.&#xD;
&#xD;
          -  Presence of active central nervous system (CNS) leukemia. Subjects adequately treated&#xD;
             for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for&#xD;
             leukemia cells are eligible. Subjects with no history of CNS leukemia will not be&#xD;
             required to undergo cerebrospinal fluid sampling for eligibility.&#xD;
&#xD;
          -  Known positive for HIV, hepatitis B virus surface antigen (HBsAg), or hepatitis C&#xD;
             virus (HCV).&#xD;
&#xD;
          -  Active infection requiring IV anti-infective usage within the last 7 days prior to&#xD;
             study treatment.&#xD;
&#xD;
          -  Any other medical intervention or condition which could compromise adherence to study&#xD;
             requirements or confound the interpretation of study results.&#xD;
&#xD;
          -  Pregnant or breast-feeding.&#xD;
&#xD;
          -  Treatment with any investigational product within 28 days prior to Screening.&#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>Guillermo Garcia-Manero, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic at Taussig Cancer Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>April 5, 2022</last_update_submitted>
  <last_update_submitted_qc>April 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute Myeloid Leukemia</keyword>
  <keyword>Chronic Myelomonocytic Leukemia</keyword>
  <keyword>Myelodysplastic Syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT02193958
org study id: FF1050101US01
nct id: NCT02193958
lead sponsor: 
has dmc: No
A Phase 1/2a Dose Escalation Study of FF-10501-01 in Patients with Relapsed or Refractory
      Hematological Malignancies to determine the safety and tolerability. A total of 6 cohorts
      will be enrolled in Phase 1 to establish the MTD. A total of 20 subjects with MDS/CMML
      treated at the RP2D are planned, including MDS/CMML subjects treated at the RP2D in Phase 1.
Subjects will receive FF-10501-01 orally on a twice daily schedule for 14, 21 or 28 days
      repeated every 28 days (=1 cycle). Disease assessments, including analysis of blood and bone
      marrow aspirates, will be performed at the end of Cycle 1 and every 2 cycles thereafter.
      Subjects who demonstrate objective response or stable disease will be allowed to continue
      therapy with FF-10501-01 until progression of disease, observation of unacceptable adverse
      events, intercurrent illness or changes in condition that prevent further study
      participation.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety assessed by adverse events
time frame: 12 months
description: Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicity (DLT), dose reductions, delays or withdrawals due to toxicity
measure: Determination of overall response rates.
time frame: Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
description: Response criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects)
measure: Evaluate the pharmacokinetic profile of FF-10501-01 and its metabolite.
time frame: Evaluated at three timepoints: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1. Each cycle is 28 days in length.
description: Cmax, Tmax, Half-life, AUC, Clearance, Volume of Distribution
measure: Changes from baseline in xanthosine monophosphate (XMP) as a pharmacodynamic marker.
time frame: Evaluated at three timepoints: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1. Each cycle is 28 days in length.
description: Xanthosine monophosphate (XMP)
measure: Evaluate the proportion of subjects who achieve hematologic improvement in peripheral blood or bone marrow blast count.
time frame: Responses and survival assessed at the end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
description: Response Criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).
measure: Evaluate progression-free survival (PFS).
time frame: Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
description: Response Criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).
measure: Evaluate overall survival (OS).
time frame: Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
description: Response criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).
arm group label: Phase 1: Lowest dose of FF-10501-01
arm group type: Experimental
description: FF-10501-01 tablets BID every 14 days of a 28 day cycle.
arm group label: Phase 1: 2x lowest dose of FF-10501-01
arm group type: Experimental
description: 2x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
arm group label: Phase 1: 4x lowest dose of FF-10501-01
arm group type: Experimental
description: 4x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
arm group label: Phase 1: 6x lowest dose of FF-10501-01
arm group type: Experimental
description: 6x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
arm group label: Phase 1: 8x lowest dose of FF-10101-01
arm group type: Experimental
description: 8x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
arm group label: Ph 2a: FF-10501-01 at 8x in MDS/CMML
arm group type: Experimental
description: FF-10501-01 tablets BID every 21 days of a 28 day cycle.
arm group label: Ph1:8x lowest dose FF10101-01 for 21 day
arm group type: Experimental
description: FF-10501-01 tablets BID every 21 days of a 28 day cycle.
arm group label: Ph1: 8x lowest dose FF-10101-01 28 day
arm group type: Experimental
description: FF-10501-01 tablets BID every 28 days of a 28 day cycle.
arm group label: Ph1: 10X lowest dose FF-10501-01 14 day
arm group type: Experimental
description: 10x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
intervention type: Drug
intervention name: FF-10501-01
description: FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle. The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.
arm group label: Ph 2a: FF-10501-01 at 8x in MDS/CMML
arm group label: Ph1: 10X lowest dose FF-10501-01 14 day
arm group label: Ph1: 8x lowest dose FF-10101-01 28 day
arm group label: Ph1:8x lowest dose FF10101-01 for 21 day
arm group label: Phase 1: 2x lowest dose of FF-10501-01
arm group label: Phase 1: 4x lowest dose of FF-10501-01
arm group label: Phase 1: 6x lowest dose of FF-10501-01
arm group label: Phase 1: 8x lowest dose of FF-10101-01
arm group label: Phase 1: Lowest dose of FF-10501-01
other name: Single Group Assignment
other name: Drug FF-10501-01
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Guillermo Garcia-Manero, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No