This is an open label, dose escalation, phase I study to determine the recommended Phase 2 dose (PR2D) by assessing the DLT, safety and efficacy of AC0010 in patients with B-cell lymphoma.
This is an open label, dose escalation, phase I study to determine the PR2D by assessing the DLT, safety and efficacy of AC0010 in patients with B-cell lymphoma. This study includes two parts. During Part 1 Dose Escalation, the "3+3" design will be applied. Dose escalation will begin at dose level 1 = 400 mg. This dose escalation will be followed by an exploratory expansion phase in 3 or 4 groups of 15\~41 patients each (CLL group, MCL group, non-germinal center B cell-like DLBCL group, and/or FL/WM(macroglobulinemia) group). The study will further evaluate the safety and efficacy of AC0010 in these patients in each group
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
184
Participants in the dose escalation cohorts will be treated with AC0010MA every 28 days
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Affiliated Hospital,Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGRecommended phase II dose
Determine the recommended phase II dose (RP2D) of AC0010 in patients with relapsed or refractory CLL/SLL, MCL, DLBCL and other Non-Hodgkin B-Cell lymphoma
Time frame: On cycle one, up to 28 days
24 hours occupancy of AC0010
AC0010 occupancy of the Bruton's tyrosine kinase (BTK) active site up to 24 hours
Time frame: 24 hours
Tolerability as measured by adverse events using CTCAE and clinical laboratory parameters
Evaluation of tolerability of AC0010 measured by number, nature and severity of Adverse Events using CTCAE Version 4.03
Time frame: Approximately 36 months
Tolerability as measured by number of subjects with dose limiting toxicities
Evaluation of tolerability of AC0010 measured by number of subjects with dose limiting toxicities (DLTs)treatment
Time frame: on cycle one, up to 28 days
Maximum tolerated dose (MTD)
Maximum Tolerated Dose (MTD) as measured by the number of dose-limiting toxicities in each dose level
Time frame: on cycle one, up to 28 days
Occupancy of AC0010 after continued treatment
AC0010 occupancy of the BTK active site after continued treatment
Time frame: On first 4 cycles,up to 4 months
Objective Response Rate (ORR)
Safety and efficacy data will take place at the analysis time point
Time frame: Approximately 36 months
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Cmax
Determine peak plasma concentration (Cmax) after oral administration of AC0010
Time frame: Day 1, Day 28, D112
Tmax
Time to reach maximum observed plasma concentration
Time frame: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112
t1/2
plasma decay half-life
Time frame: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112
AUC(0-t)
Area under the curve from time zero to the last quantifiable concentration
Time frame: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112
AUC(0-∞)
Area under the curve from time zero to extrapolated infinity
Time frame: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112