This is an open-label, non-randomized, Phase 1b study to evaluate the safety, pharmacokinetics (PK) profiles, and preliminary evidence of antitumor activity of PTC299 and the metabolite, O-desmethyl PTC299, in participants with relapsed/refractory acute myeloid leukemia (AML) who have exhausted standard available therapies known to provide clinical benefit. The study is designed as a series of cohort-based dose escalations. For each cohort, a minimum of 3 evaluable participants with PK and safety data will be assessed. Additional participants will be recruited if additional PK data are needed to assess mean exposure based on the observed variability.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
PTC299 will be administered per the treatment arm description
Rocky Mountain Cancer Center
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
Henry Ford Health System
Detroit, Michigan, United States
Rutgers, Cancer Institute of NJ
New Brunswick, New Jersey, United States
Columbia
New York, New York, United States
University of Rochester MC
Rochester, New York, United States
Duke Cancer Center
Durham, North Carolina, United States
Gabrail Cancer Center
Canton, Ohio, United States
Oncology Hematology Care, Inc.
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
...and 7 more locations
Number of Participants Who Discontinued Study Drug Due to Adverse Event (AE)
Time frame: From Screening to 50 days post treatment
Time to Maximum Plasma Concentration (Tmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Maximum Plasma Concentration (Cmax) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Area Under the Concentration-Time Curve (AUC) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Half-life (t1/2) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Estimate t1/2 of of both PTC299 and O-desmethyl PTC299 During 14-Day Washout Period
Time frame: Day 29 through Day 42
Apparent Clearance (CL/F) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Apparent Volume of Distribution (Vz/F) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Accumulation Ratio (R) of both PTC299 and O-desmethyl PTC299 when PTC299 is Given as Tablet with Food
Time frame: Days 1, 15, 28, 57, 71 and 99
Percentage of Participants Achieving Response Rate/Overall Response Rate Utilizing International Working Group (IWG) Response Criteria for AML
Time frame: Up to 6 Months
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