This study is a multi-center, open-label, single-arm phase I clinical study of LP-108. Patients with relapsed or refractory chronic lymphocytic leukemia (CLL, arm A) and other B cell non-Hodgkin's lymphoma (NHL, Arm B). Each arm has a dose escalation phase (phase Ia) and expansion phase (phase Ib). During the dose escalation phase, the primary objectives are to define dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and to explore a recommended phase II dose. Dose escalation is based on the classic "3 + 3" design, while accelerated titration is applied to the initial lower doses. After the RP2Ds are determined, additional patients will be enrolled in the expansion phase to further evaluation the safety, PK and preliminary efficacy of LP-108, each therapy can enroll 12-20 subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
74
Taken orally within 30 minutes after a meal at the designated dose, once daily.
the First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
RECRUITINGDetermination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RP2D), and lead-in period regimen
Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
Time frame: Lead-in period (0-4 weeks) plus 3 weeks of study drug administration at the designated cohort dose.
Number of subjects with adverse events and its frequency
Safety Proflie
Time frame: From first dose of study drug administration until 30 days after study drug discontinue.
Determination of plasma peak concentration (Cmax) of LP-108
Blood and urine samples for pharmacokinetic analysis of LP-108 will be collected at designated time points.
Time frame: Up to Week 37 for LP-108.
Determination of Area Under the Curve (AUC) of LP-108
Blood and urine samples for pharmacokinetic analysis of LP-108 will be collected at designated time points.
Time frame: Up to Week 37 for LP-108.
Food Effect - Cmax
Blood samples for food effect pharmacokinetic analysis of LP-108 will be collected at designated time points
Time frame: Pharmacokinetic (PK) parameter Cmax (maximum plasma concentration of LP-108) between each diet (LP-108 under fasting versus fed conditions),up to week 8 for LP-108.
Food Effect - AUC
Blood samples for food effect pharmacokinetic analysis of LP-108 will be collected at designated time points
Time frame: Pharmacokinetic (PK) parameter AUC (area under the curve of LP-108) between each diet (LP-108 under fasting versus fed conditions),up to week 8 for LP-108.
Preliminary efficacy assessment
Tumor response or clinical disease progression
Time frame: Designated dose starting week for clinical disease progression and tumor response; and every 4-12 weeks thereafter until the date of first documented progression or date of death from any cause, whichever came first,.assessed up to 24 months.
Minimal residual disease (MRD)
MRD assessed in the peripheral blood and/or bone marrow (BM) either by four color flow cytometry or NGS, will be measured in CLL subjects achieving CR/CRi.
Time frame: At least 2 months after the CR, CRi criteria for tumor response are first met. Measured up to 24 months after the last subject has enrolled in the study.
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