Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
- Registration Number
- NCT03194685
- Lead Sponsor
- Fujifilm Pharmaceuticals U.S.A., Inc.
- Brief Summary
A Phase 1 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: 10 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 2: 20 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 3: 35 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 4: 50 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 5: 75 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 6: 100 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 7: 150 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01 Cohort 8: 225 mg FF-10101-01 Orally once a day (QD) on Days 1-28 of a 28-day cycle. Drug: FF-10101-01
- Primary Outcome Measures
Name Time Method Phase 1: Frequency of adverse events 12 months Safety Assessments include frequency of adverse events (AEs) in percentage (%)
- Secondary Outcome Measures
Name Time Method 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)) 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 - Maximum observed concentration (Cmax) 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) 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 -Plasma concentration-time curve (AUC(0-last)) 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) 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) 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 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 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 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) 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) 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 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 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) Cycle 1, Day 1 through Cycle 2, Day 1 Metabolite (FF-10101M1) to parent (FF-10101) exposure ratios for AUC(τ)
Phase 1: Frequency of Serious Adverse Events 12 Months Safety Assessments include frequency of Serious adverse events (SAEs)
Phase 1: Frequency of Dose Limiting Toxicities 12 Months Safety Assessments include frequency of dose-limiting toxicities (DLTs), dose reductions, delays, or withdrawals due to toxicity.
Phase 1: Frequency of adverse events including assessment of Hematology laboratory parameters 12 Months Safety assessments also include assessment of clinical laboratory parameters Hematology
Phase 1: Frequency of adverse events including assessment of serum chemistry laboratory parameters 12 Months Safety assessments also include assessment of clinical laboratory parameters serum chemistry
Phase 1: Frequency of adverse events including assessment of urinalysis laboratory parameters 12 Months Safety assessments also include assessment of clinical laboratory parameters urinalysis
Phase 1: Frequency of Adverse events including assessment of vital signs 12 Months Safety assessments also include assessment of Vital signs (Heart Rate and BP)
Phase 1: Frequency of Adverse events including assessment of vital signs - Heart Rate 12 Months Safety assessments also include assessment of Vital signs Heart Rate
Phase 1: Frequency of Adverse events including assessment of vital signs - Blood Pressure 12 Months Safety assessments also include assessment of Vital signs BP)
Phase 1: Frequency of Adverse events including assessment of 12 lead ECG. 12 Months Safety assessments also include assessment of 12 lead ECG.
Phase 1: Composite complete remission rate (CRc) including CR 12 Months Composite complete remission rate (CRc) which includes CR
Phase 1: Composite complete remission rate (CRc) including CR with incomplete platelet recovery (CRp) 12 Months Composite complete remission rate (CRc) which includes CR with incomplete platelet recovery (CRp)
Phase 1: Composite complete remission rate (CRc) including CR with incomplete neutrophil recovery with or without platelet recovery (CRi)) 12 Months Composite complete remission rate (CRc) which includes CR with incomplete neutrophil recovery with or without platelet recovery (CRi))
Trial Locations
- Locations (7)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of California Los Angeles, David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
University Of California, San Francisco School of Medicine
🇺🇸San Francisco, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Johns Hopkins Hospital - Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States