This is a Phase I, multi-center, open-label, FIH study comprising of 2 study parts (Phase Ia, Phase Ib). The Phase Ia (dose escalation) part of the study is designed to determine the safety, tolerability, and maximum tolerated dose (MTD)/recommended dose for expansion (RP2D) of BR101801 in subjects with relapsed/refractory B cell lymphoma, chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), and peripheral T cell lymphoma (PTCL). The Phase Ib (dose expansion) part of the study is designed to assess tumor response and safety in specific advanced relapsed/refractory Peripheral T-cell lymphoma(PTCL) at a dose of BR101801 identified in Phase Ia. Once the RP2D has been determined in Phase Ia (dose escalation), Phase Ib (dose expansion) will commence.
1. Phase Ia (Dose Escalation) Primary Objectives * To assess the safety and tolerability of BR101801 in patients with relapsed/refractory B-cell lymphoma, CLL/SLL, and PTCL. * To assess DLT and to determine the MTD and/or the RDE dose for BR101801 when administered orally on a daily schedule in 4-week cycles until disease progression. SecondaryObjectives * To characterize the plasma and urine PK of BR101801. * To assess the preliminary antitumor activity of BR101801. 2. Phase Ib (Dose Expansion) Primary Objectives • To assess the safety and tolerability of BR101801 at the RP2D dose in subjects with relapsed/refractory Peripheral T-cell lymphoma (PTCL). SecondaryObjectives * To assess clinical activity of BR101801 when administered orally on a daily schedule in 4-week cycles until disease progression. * To assess the plasma PK of BR101801. OUTLINE: This is a Phase I, multi-center, open-label, FIH study. The safety monitoring committee(SMC) will be responsible for safety oversight.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Phase Ia (dose escalation):25 mg capsules and 100 mg capsules Planned doses are 50, 100, 200, 325, and 450 mg.
Phase Ib (dose expansion):25 and 100 mg capsules Doses administered will be determined from Phase Ia data.
Henry Ford Hospital
Detroit, Michigan, United States
National Cancer Center
Goyang-si, Gyeonggi-do, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, South Korea
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, South Korea
Inje University Busan Paik Hospital
Busan, South Korea
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul national university hospital
Seoul, South Korea
Severance Hospital, Yonsei University Health System
Seoul, South Korea
To determination of the MTD and RDE based on DLTs during Cycle 1 (Phase Ia)
The recommended dose is determined by the number of patients who experience a dose limiting toxicity (DLT).
Time frame: From baseline to Week 4
Number of participants with adverse events (AE) as a measure of safety and tolerability of BR101801 when administered at the MTD or recommended dose (Phase Ia and Ib)
To evaluate safety and tolerability the aggregate review will include but is not limited to: * CTCAE TEAEs, treatment-related TEAEs, Grade 3 or higher TEAEs, Grade 3 or higher treatment-related TEAEs, serious treatment-related TEAEs, and TEAEs leading to death. * Laboratory results; * Vital signs; * ECGs; * Physical examination * ECOG performance status
Time frame: through study completion, and about average of 1 year
Cmax
Maximum concentration obtained directly from the observed concentration versus time data.
Time frame: Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15
AUC(0-inf)
Area under the plasma concentration-time curve from time zero extrapolated to infinity, calculated by linear up/log down trapezoidal summation
Time frame: Cycle1( each cycle is 28 days) Day 1
AUC(0-last)
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Time frame: Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15, Pre-dose to 24 hours after dosing
AUC(0-tau)
Area under the plasma concentration-time curve from time zero during a dosing interval
Time frame: Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15, dosing interval: 24 or 12 hours
Ae
Cumulative amount of unchanged drug excreted in urine
Time frame: Cycle 1( each cycle is 28 days)Day 15, Pre-dose to 12 hours for BID dosing and Pre-dose to 24 hours for QD dosing
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