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Trial record 1 of 1 for:    FF-10101
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Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03194685
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
Fujifilm Pharmaceuticals U.S.A., Inc.

Tracking Information
First Submitted Date  ICMJE May 4, 2017
First Posted Date  ICMJE June 21, 2017
Last Update Posted Date October 9, 2019
Actual Study Start Date  ICMJE May 5, 2017
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
Phase 1/2a: Frequency of adverse events [ Time Frame: 12 months ]
Safety Assessments include frequency of adverse events (AEs) in percentage (%)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
  • Phase 2a Clinical response of FF-10101-01 to AML [ Time Frame: Response and survival assessments at the beginning Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1 and every 3 months for 2 year ]
    RFS: Defined as the time from CR to recurrence or death due to any cause. DOR: Defined as time from CR, CRp or CRi to recurrence. OS: Defined as time from the first FF-10101-01 administration to the time of death, censored (if appropriate) at the date last known to be alive. Recurrence (Relapse after confirmed CR): Reappearance of leukemia blats in peripheral blood or ≥5% blasts in the bone marrow not attributable in the Investigator's opinion to any other cause (e.g., bone marrow regeneration after consolidation therapy) or appearance of new dysplastic changes. PR: Defined as ≥50% decrease in bone marrow blasts to 5% to 25 % abnormal cells in the bone marrow, or CR with ≤5% blasts if Auer rods are present Treatment failure: defined as failure to achieve CR, CRi, CRp or PR
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Maximum observed concentration (Cmax) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Maximum observed concentration (Cmax)
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Time to maximum concentration (tmax) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Time to maximum concentration (tmax)
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Area under the plasma concentration-time curve in the sampled matrix during a 24-hour dosing interval (AUC(τ)) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Area under the plasma concentration-time curve in the sampled matrix during a 24-hour dosing interval (AUC(τ))
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite -Plasma concentration-time curve (AUC(0-last)) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Area under the plasma concentration-time curve in the sampled matrix from time zero to the last quantifiable concentration, if concentrations are not quantifiable over the entire 24-hour dosing interval (AUC(0-last))
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Dose normalized AUC(τ) (AUC(τ)/dose) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Dose normalized AUC(τ) (AUC(τ)/dose)
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Dose normalized Cmax (Cmax/dose) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Dose normalized Cmax (Cmax/dose)
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Accumulation ratio for AUC [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Accumulation ratio for AUC [RaccAUC ie, ratio of Day 29/Day 1 of the PK parameter]
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Accumulation ratio for Cmax [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Accumulation ratio for Cmax [RaccCmax ie, ratio of Day 29/Day 1 of the PK parameter]
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Oral clearance (CL/F) for FF-10101 [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Oral clearance (CL/F) for FF-10101
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Average concentrations (Cavg) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Average concentrations (Cavg)
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Minimum observed concentration (Cmin) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Minimum observed concentration (Cmin)
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Fluctuation index [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Fluctuation index
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Metabolite (FF-10101M1) to parent (FF-10101) exposure ratios for Cmax [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Metabolite (FF-10101M1) to parent (FF-10101) exposure ratios for Cmax
  • Phase 1: Evaluate the Pharmacokinetic profile of FF-10101-01 and its Metabolite - Metabolite (FF-10101M1) to parent (FF-10101) exposure ratios for AUC(τ) [ Time Frame: Cycle 1, Day 1 through Cycle 2, Day 1 ]
    Metabolite (FF-10101M1) to parent (FF-10101) exposure ratios for AUC(τ)
  • Phase 1/2a: Frequency of Serious Adverse Events [ Time Frame: 12 Months ]
    Safety Assessments include frequency of Serious adverse events (SAEs)
  • Phase 1/2a: Frequency of Dose Limiting Toxicities [ Time Frame: 12 Months ]
    Safety Assessments include frequency of dose-limiting toxicities (DLTs), dose reductions, delays, or withdrawals due to toxicity.
  • Phase 1/2a: Frequency of adverse events including assessment of Hematology laboratory parameters [ Time Frame: 12 Months ]
    Safety assessments also include assessment of clinical laboratory parameters Hematology
  • Phase 1/2a: Frequency of adverse events including assessment of serum chemistry laboratory parameters [ Time Frame: 12 Months ]
    Safety assessments also include assessment of clinical laboratory parameters serum chemistry
  • Phase 1/2a: Frequency of adverse events including assessment of urinalysis laboratory parameters [ Time Frame: 12 Months ]
    Safety assessments also include assessment of clinical laboratory parameters urinalysis
  • Phase 1/2a: Frequency of Adverse events including assessment of vital signs [ Time Frame: 12 Months ]
    Safety assessments also include assessment of Vital signs (Heart Rate and BP)
  • Phase 1/2a: Frequency of Adverse events including assessment of vital signs - Heart Rate [ Time Frame: 12 Months ]
    Safety assessments also include assessment of Vital signs Heart Rate
  • Phase 1/2a: Frequency of Adverse events including assessment of vital signs - Blood Pressure [ Time Frame: 12 Months ]
    Safety assessments also include assessment of Vital signs BP)
  • Phase 1/2a: Frequency of Adverse events including assessment of 12 lead ECG. [ Time Frame: 12 Months ]
    Safety assessments also include assessment of 12 lead ECG.
  • Phase 1/2a: Composite complete remission rate (CRc) including CR [ Time Frame: 12 Months ]
    Composite complete remission rate (CRc) which includes CR
  • Phase1/2a: Composite complete remission rate (CRc) including CR with incomplete platelet recovery (CRp) [ Time Frame: 12 Months ]
    Composite complete remission rate (CRc) which includes CR with incomplete platelet recovery (CRp)
  • Phase1/2a: Composite complete remission rate (CRc) including CR with incomplete neutrophil recovery with or without platelet recovery (CRi)) [ Time Frame: 12 Months ]
    Composite complete remission rate (CRc) which includes CR with incomplete neutrophil recovery with or without platelet recovery (CRi))
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official Title  ICMJE A First-in-Human Phase 1/2a Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of FF-10101-01 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia
Brief Summary A Phase 1/2a dose escalation and dose ranging study of FF-10101-01 in subjects with relapsed or refractory acute myeloid leukemia to determine the safety, tolerability, PK and preliminary efficacy. A total of 9 cohorts will be enrolled in Phase 1 to establish the Maximum Tolerated Dose (MTD). Phase 2a will consist of up to 3 dose levels (high, medium, and low) of which subjects with FLT3 mutations will randomly be assigned.
Detailed Description

Subjects will receive FF-10101-01 orally once a day repeated every 28 days =1 cycle Frequent blood draws will be collected to measure pharmacodynamic parameters and pharmacodynamic activity.

Disease assessments, including bone marrow aspirates, will be performed at the beginning of cycles 1-3, and every 3 months thereafter. Subjects who demonstrate objective response or stable disease will be allowed to continue therapy with FF-10101-01 until , observation of unacceptable adverse events, or until the subject is no longer deriving benefit based on the opinion of the investigator.

For Phase 2a long term phone follow-up for assessment of overall survival will also occur.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:
Open Label
Primary Purpose: Treatment
Condition  ICMJE AML, Adult
Intervention  ICMJE Drug: FF-10101-01
FF-10101-01 will be administered orally once a day on Days 1-28 of a 28-day cycle. In Phase 1, the dose escalation will proceed until MTD is reached. In Phase 2a, subjects will be randomly assigned to 1 of 3 dose levels in a balanced fashion. The treatment will continue until, intolerable toxicity, or investigation/subject decision.
Other Name: FF-10101 succinate
Study Arms  ICMJE
  • Experimental: Phase 1 Cohort 1: 10 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 2: 20 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 3: 35 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 4: 50 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 5: 75 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 6: 100 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 7: 150 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 8: 225 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 1 Cohort 9: 300 mg
    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 . The dose escalation will proceed until MTD is reached.
    Intervention: Drug: FF-10101-01
  • Experimental: Phase 2a Group 1: High Dose

    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 .

    Phase 2a, subjects will be randomly assigned to 1 of 3 dose levels in a balanced fashion. The treatment will continue until disease progression, intolerable toxicity, or investigation/subject decision.

    Intervention: Drug: FF-10101-01
  • Experimental: Phase 2a Group 2: Middle Dose

    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 .

    Phase 2a, subjects will be randomly assigned to 1 of 3 dose levels in a balanced fashion. The treatment will continue until disease progression, intolerable toxicity, or investigation/subject decision.

    Intervention: Drug: FF-10101-01
  • Experimental: Phase 2a Group 3: Low Dose

    Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 .

    Phase 2a, subjects will be randomly assigned to 1 of 3 dose levels in a balanced fashion. The treatment will continue until disease progression, intolerable toxicity, or investigation/subject decision.

    Intervention: Drug: FF-10101-01
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2017)
99
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subjects who are able and willing to give written informed consent

  • Documented primary or secondary AML, as defined by the WHO criteria (2008), by histopathology refractory to previous induction chemotherapy and/or relapsed after achieving remission with a prior chemotherapy and who are not candidates for other available therapy likely to confer clinical benefit.
  • For Phase 2a only: in addition to inclusion criteria 2 above, patients must have a FLT3 mutation of any type
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • In the absence of rapidly progressing disease, the interval from prior treatment to time of FF-10101-01 administration should be at least 14 days for cytotoxic agents other than hydroxyurea, at least 5 half-lives for non-cytotoxic agents, and 14 days for monoclonal antibody therapies. Hydroxyurea may be continued for a maximum of 14 days from the start of FF-10101-01 dosing, through Cycle 1 Day 14, with a maximal dose of 5 grams/day
  • Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be ≤Grade 2
  • If subject has had a hematopoietic stem cell transplant, subject must be ≥60 days post-transplant with no clinically significant GVHD requiring systemic therapy
  • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 times the upper limit of normal and total bilirubin of ≤1.5x the upper limit of normal. If total bilirubin is equal to or exceeds 1.5x the upper limit of normal, the subject can still be included if direct bilirubin is ≤1.5x the upper limit of normal
  • Calculated creatinine clearance of ≥60 mL/min
  • Female subjects of childbearing potential and sexually mature male subjects must agree to use a medically accepted method of contraception other than an oral contraceptive for the duration of the study.

Exclusion Criteria:

  • Subjects diagnosed with acute promyelocytic leukemia
  • Subjects with Bcr-Abl positive leukemia (chronic myelogenous leukemia in blast crisis)
  • Subjects with clinically active CNS leukemia
  • Subjects with major surgery within 28 days prior to the first administration of FF-10101-01
  • Subjects with radiation therapy within 28 days prior to the first administration of FF-10101-01
  • Subjects with active malignant disease requiring therapy other than AML or myelodysplastic syndrome with transformation into AML
  • Subjects with an active uncontrolled infection
  • Subjects with a medical condition, serious intercurrent illness, or other circumstance that, in the Investigator's judgment, could jeopardize the subject's safety as a study subject, or that could interfere with the study objectives
  • Subjects known to have human immunodeficiency virus infection, or who have active hepatitis B or C infection as determined by serological testing
  • Subjects with congestive heart failure, New York Heart Association (NYHA) Class 3 or 4, or subjects with a past history of congestive heart failure NYHA Class 3 or 4 and in whom echocardiogram or multiple gate acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a LVEF <40%
  • Female subjects who are pregnant or breast feeding
  • Subjects on 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) or other drugs known to have muscle toxicity
  • Subjects taking strong inhibitors of CYP3A4 will be excluded from the study unless therapeutic substitution is possible
  • Subjects taking strong inducers of CYP3A4 will be excluded from the study unless therapeutic substitution is possible
  • Use of systemic immunosuppressive agents within 14 days prior to first dose of FF-10101
  • Subjects taking drugs known to cause Torsades de Pointes will be excluded from the study unless therapeutic substitution is possible
  • Subjects known to have long QT syndrome
  • Subjects with mean QTcF values following 3 ECGs conducted 5 minutes apart of >470 msec
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Coordinator fphucontact@fujifilm.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03194685
Other Study ID Numbers  ICMJE FF-10101-US101/201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Fujifilm Pharmaceuticals U.S.A., Inc.
Study Sponsor  ICMJE Fujifilm Pharmaceuticals U.S.A., Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fujifilm Pharmaceuticals U.S.A., Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP