Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL
A Phase Ib/II Study of 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
1 other identifier
interventional
123
1 country
18
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2020
Longer than P75 for phase_1
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 21, 2020
CompletedFirst Posted
Study publicly available on registry
July 31, 2020
CompletedStudy Start
First participant enrolled
August 31, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 20, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2025
CompletedApril 16, 2025
April 1, 2025
4.1 years
July 21, 2020
April 15, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Adverse events of APG-2575 single agent
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
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.
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.
28 days.
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)
MTD/RP2D will be determined based on DLTs observed during cycle one.
28 days.
Secondary Outcomes (5)
Maximum plasma concentration (Cmax)
28 days.
Area under the plasma concentration versus time curve (AUC)
28 days.
Objective Response Rate (ORR) of APG-2575 combination therapy
Up to 6 cycles (each cycle is 28 days).
Minimal residual lesions (MRD) of peripheral blood and/or bone marrow.
2 years.
Survival benefit (PFS) of APG-2575 combination therapy
2 years.
Study Arms (3)
APG-2575 single agent in Relapse/Refractory CLL/SLL
EXPERIMENTALAPG-2575 orally once daily at 400mg, 600mg, 800mg dose levels respectively, every 28 days as a cycle.
APG-2575+Rituximab in Relapse/Refractory CLL/SLL
EXPERIMENTALStage 1:APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg. Rituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1. Every 28 days as a cycle. Stage 2: APG-2575 MTD/RP2D combined with rituximab. Every 28 days as a cycle.
APG-2575+ibrutinib in Relapse/Refractory CLL/SLL
EXPERIMENTALStage 1: APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg.Ibrutinib 420mg orally once daily during C1D8-28 and following cycles. Every 28 days as a cycle. Stage 2: APG-2575 MTD/RP2D combined with ibrutinib. Every 28 days as a cycle.
Interventions
APG-2575 orally once daily, every 28 days as a cycle.
Rituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1.
Ibrutinib 420mg orally once daily during C1D8-28 and following cycles.
Eligibility Criteria
You may qualify if:
- Age ≥18 years old.
- Diagnosis as relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma according to the IWCLL NCI-WG guidelines revised in 2008.
- Through radiological assessment, subjects with a lymph node length ≥ 10 cm require prior approval from the sponsor before enrollment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1.
- QTcF interval ≤450ms in males, and ≤470ms in females.
- Adequate bone marrow function independent of growth factor and transfusion.
- Adequate renal and liver function.
- Willingness by males, female patients of child bearing potential, and their partners to use contraception by effective methods throughout the treatment period and for at least three months following the last dose of study drug.
- Pregnancy test results of serum samples obtained within 14 days before the first study drug administration in fertile female subjects were negative; If the serum pregnancy test results obtained are\> 7 days from the first administration, urine sample obtained before the first study dose of study drug must be negative.
- Male subjects must avoid sperm donation throughout the treatment period and for at least three months following the last dose of study drug.
- Ability to understand and willingness to sign a written informed consent form approved by EC committee (the consent form must be signed by the patient prior to any screening or study-specific procedures).
- Willingness and ability to comply with study procedures and follow-up examination.
You may not qualify if:
- Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cell immunotherapy within 24 months or autologous hematopoietic stem cell transplantation within 12 months.
- Monoclonal antibody therapy against CLL was adopted within 4 weeks prior to the first dose of the study drug.
- Receive any of the following treatments within 14 days or 5x half-life before the first dose of study drug, or clinically significant adverse reactions / toxicities due to previous treatments have not recovered to ≤ Grade 1: Anti-tumor therapies include chemotherapy, radiotherapy, anti-tumor steroid treatment, anti-tumor Chinese medicine treatment; investigational treatment, including targeted small molecule drugs.
- Use the following drugs within 14 days before the first dose of study drug: moderately potent CYP3A inhibitors such as fluconazole, ketoconazole and clarithromycin; moderately potent CYP3A inducers such as rifampin, carbamazepine, phenytoin And St. John's wort.
- Failure to recover adequately, at the discretion of the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
- Received Bcl-2 inhibitor treatment.
- Invasive NHL transformation or central nervous system (CNS) involvement. has occurred.
- Cardiovascular disease of grade ≥2 (New York Heart Association Class).
- A significant history of renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular or liver disease. The investigator believes that participating in this study will have an adverse effect on him / her. For subjects requiring intervention for any of the above diseases in the past 6 months, the investigator and the sponsor must discuss.
- Warfarin or other anticoagulants is required.
- Known to be allergic to study drug ingredients or their analogues.
- Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment.
- Within 3 years before entering the study, the subject had a history of active malignant tumors other than CLL / SLL, except that:
- Fully treated cervical carcinoma in situ;
- Completely resected basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Peking University Third Hospital
Beijing, Beijing Municipality, China
Chongqing Cancer Hospital
Chongqing, Chongqing Municipality, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Guangxi Medical University Affiliated Tumor Hospital
Nanning, Guangxi, China
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
Henan Provincial Oncology Hospital
Zhenzhou, Henan, China
Union Hospital medical college Huazhong University of Science and Technology
Wuhan, Hubei, China
Xiangya Hospital Central South University
Changsha, Hunan, China
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
Zhongda Hospital Southeast University
Nanjing, Jiangsu, China
The First affiliated hospital of Soochow University
Suzhou, Jiangsu, China
The First affiliated hospital of Nanchang University
Nanchang, Jiangxi, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Fudan University Zhongshan Hospital
Shanghai, Shanghai Municipality, China
Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
The First Bethune Hospital of Jilin University
Hangzhou, Zhejiang, China
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Yifan Zhai, M.D., Ph.D.
yzhai@ascentage.com
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2020
First Posted
July 31, 2020
Study Start
August 31, 2020
Primary Completion
October 20, 2024
Study Completion
December 1, 2025
Last Updated
April 16, 2025
Record last verified: 2025-04