RO6870810 (formerly TEN-010) is a small molecule, bromodomain and extra-terminal (BET) bromodomain inhibitor. This study is designed to characterize the safety, tolerability, and pharmacokinetics of RO6870810 monotherapy in participants with relapsed/refractory acute myeloid leukemia (RR-AML) and hypomethylating agent (HMA)-refractory myelodysplastic syndrome (MDS). The study will consist of a Screening Period, Treatment Period, and Post-Treatment Period. A standard 3+3 design will be used in which successive cohorts of three or more participants with RR-AML or HMA-refractory MDS will be treated at escalating doses until a maximum tolerated dose (MTD) is identified. Up to 51 adult participants with AML or MDS will be enrolled in the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Participants will receive RO6870810 once daily (at escalated doses) via subcutaneous injection in either 28-day cycles (continuous 28 days dosing or 21 days dosing followed by 7 days off drug) or in 21-day cycle (14 days dosing followed by 7 days off drug), until MTD is identified.
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Weill Cornell Medical College
New York, New York, United States
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 (cycle length = 21 or 28 days)
MTD of RO6870810
Time frame: Cycle 1 (cycle length = 21 or 28 days)
Percentage of Participants With Adverse Events (AEs)
Time frame: Baseline up to 30 days after last dose (up to approximately 2.75 years)
Area Under the Concentration Versus Time Curve from Time Zero to the End of Dosing Interval 24 Hours Later (AUC0-24) of RO6870810
Predose (Hour 0), immediately postdose and 0.25, 0.5, 1, 2, 4 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 22 (Cycle 1 Day 22 is applicable only for 28-day continuous treatment); Predose (Hour 0), 4 hours postdose on Cycle 1 Day 2; Days 8, 15 of Cycle 1; Predose (Hour 0) on Day 1 of each treatment cycle from Cycle 2 up to end of treatment (approximately 2.75 years) (Cycle length = 21 or 28 days)
Time frame: Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
Maximum Observed Plasma Concentration (Cmax) of RO6870810
Predose (Hour 0), immediately postdose and 0.25, 0.5, 1, 2, 4 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 22 (Cycle 1 Day 22 is applicable only for 28-day continuous treatment); Predose (Hour 0), 4 hours postdose on Cycle 1 Day 2; Days 8, 15 of Cycle 1; Predose (Hour 0) on Day 1 of each treatment cycle from Cycle 2 up to end of treatment (approximately 2.75 years) (Cycle length = 21 or 28 days)
Time frame: Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
Time to Cmax (Tmax) of RO6870810
Predose (Hour 0), immediately postdose and 0.25, 0.5, 1, 2, 4 hours postdose on Cycle 1 Day 1 and Cycle 1 Day 22 (Cycle 1 Day 22 is applicable only for 28-day continuous treatment); Predose (Hour 0), 4 hours postdose on Cycle 1 Day 2; Days 8, 15 of Cycle 1; Predose (Hour 0) on Day 1 of each treatment cycle from Cycle 2 up to end of treatment (approximately 2.75 years) (Cycle length = 21 or 28 days)
Time frame: Cycle 1 Day 1 up to 2.75 years (detailed timeframe is provided in outcome description)
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