The purpose of this study is to assess the safety, pharmacokinetic, pharmacodynamic and efficacy of APG-2575 single agent and in combination with other therapeutic agents in patients with relapsed/refractory CLL/SLL.
This is an open-label, multi-center Phase Ib/II study of safety, PK, PD and efficacy of APG-2575 as a single agent or in combination with rituximab or ibrutinib in relapsed/refractory CLL/SLL patients. This study consists of two parts: The first part is the APG-2575 single agent cohort expansion. The cohort expansion will be conducted at three dose levels of 400 mg, 600 mg, and 800 mg. And up to 15 patients are planned to be enrolled at each dose level. The second part contains two arms: APG-2575 combined with rituximab (Arm A) and APG-2575 combined with ibrutinib (Arm B). Both the two arms consist of two stages: dose escalation stage (first stage) and dose expansion stage (second stage). The first stage is the study of APG-2575 dose escalation combined with rituximab/ibrutinib. APG-2575 dose escalates according to the standard 3+3 design, the initial dose is 200mg, the dose of APG-2575 will be increased in subsequent levels, to 400mg, 600mg, 800mg respectively. The second stage is the MTD/RP2D expansion stage. Once the respective MTD/RP2D of arms A and B is determined, up to 15 subjects in each MTD/RP2D dose level would be enrolled. APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycle. Rituximab, on cycle 1 day 8(C1D8): 375mg/m2; on cycles 2-6 day l(C2-6D1): 500mg/m2, a total of six infusions. Ibrutinib 420 mg will be orally administered daily beginning from cycle 1 day 8 and continuously thereafter, every 4 weeks as a cycle.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
123
Peking University Third Hospital
Beijing, Beijing Municipality, China
RECRUITINGAdverse events of APG-2575 single agent
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Time frame: Up to 6 cycles (each cycle is 28 days).
Objective Response Rate (ORR) of APG-2575 single agent
ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.
Time frame: Up to 6 cycles (each cycle is 28 days).
Dose Limiting Toxicities (DLT) of combination therapy
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
Time frame: 28 days.
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)
MTD/RP2D will be determined based on DLTs observed during cycle one.
Time frame: 28 days.
Maximum plasma concentration (Cmax)
Cmax of APG-2575 will be assessed in the patients in single agent or combo study. Cmax of ibrutinib will be assessed in the patients treated with APG-2575 combination with ibrutinib.
Time frame: 28 days.
Area under the plasma concentration versus time curve (AUC)
AUC of APG-2575 will be assessed in the patients in single agent or combo study. AUC of ibrutinib will be assessed in the patients treated with APG-2575 combination with ibrutinib.
Time frame: 28 days.
Objective Response Rate (ORR) of APG-2575 combination therapy
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Chongqing Cancer Hospital
Chongqing, Chongqing Municipality, China
RECRUITINGNanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
RECRUITINGGuangxi Medical University Affiliated Tumor Hospital
Nanning, Guangxi, China
RECRUITINGThe Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
RECRUITINGThe Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
RECRUITINGHenan Provincial Oncology Hospital
Zhenzhou, Henan, China
RECRUITINGUnion Hospital medical college Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGXiangya Hospital Central South University
Changsha, Hunan, China
RECRUITINGThe First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
RECRUITING...and 8 more locations
ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.
Time frame: Up to 6 cycles (each cycle is 28 days).
Minimal residual lesions (MRD) of peripheral blood and/or bone marrow.
Time frame: 2 years.
Survival benefit (PFS) of APG-2575 combination therapy
PFS,Time from the beginning of treatment to the first occurrence of Progressive Disease (PD) or death.
Time frame: 2 years.