Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL
- Conditions
- Small Lymphocytic LymphomaChronic Lymphocytic Leukemia
- Interventions
- Drug: APG2575
- Registration Number
- NCT05147467
- Lead Sponsor
- Ascentage Pharma Group Inc.
- Brief Summary
The purpose of this study is to assess the efficacy and safety of APG-2575 single agent in patients with relapsed/refractory CLL/SLL.
- Detailed Description
This is an single-arm, open-label, multi-center, pivotal registration Phase II study of efficacy and safety of APG-2575 as a single agent in relapsed/refractory CLL/SLL patients.
This study plans to enroll approximately 75 CLL/SLL subjects who have failed or are intolerant to prior immunochemotherapy and BTK inhibitor therapy. Eligible subjects will receive APG-2575 600mg, orally administered once daily (QD), within half an hour of a low-fat meal, for a cycle of 28 days. Participants will continue to accept APG - 2575 until the "end of treatment" that are consistent with the provisions in the solution of the termination of any specified standards.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
Subjects who meet each of the following inclusion criteria are eligible to participate in this study:
- Age ≥18 years old.
- Pathologically confirmed CLL/SLL according to the 2018 revised IWCLL NCI-WG guidelines, subject with measurable lesions or splenomegaly due to CLL.
- Expected survival is at least 12 weeks.
- Refractory, recurrent, or intolerant to BTK inhibitors and immunochemotherapy,or first-line treatment with BTK inhibitors fails and is not suitable for immunochemotherapy.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2.
- 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.
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
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Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cell immunotherapy or autologous hematopoietic stem cell transplantation within 24 months.
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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.
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Received Bcl-2 inhibitor treatment.
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Invasive NHL transformation or central nervous system (CNS) involvement has occurred.
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Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment.
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Within 2 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;
- Confinement and resection of previously cured malignancies (or other treatment).
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Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for participation in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description APG-2575 single agent in Relapse/Refractory CLL/SLL APG2575 APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to 9 months after the last subject enrolled. ORR is defined by Complete Remission (CR)+ CR with incomplete marrow recovery (CRi) + Partial Remission (PR) (according to NCI-WG CLL(2018)) and by CR+PR ( according to Lugano (2014)).Response will be evaluated every 2 cycles (8 weeks) till complete treatment or one month after last dose.
- Secondary Outcome Measures
Name Time Method Time To Progression (TTP) Up to 9 months after the last subject enrolled. TTP is defined as the time from the first administration to PD.
Area under the plasma concentration versus time curve (AUC) Up to 4 cycles (each cycle is 28 days). Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-2575 treatments.
Maximum plasma concentration (Cmax) Up to 4 cycles (each cycle is 28 days). Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2575 treatments.
Overall Survival (OS) Up to 9 months after the last subject enrolled. OS is defined as the time from the first administration to death.
Progress Free Survival (PFS) Up to 9 months after the last subject enrolled. PFS is defined as the time from the first administration to disease progression(PD) or death from any cause.
Time To Response (TTR) Up to 9 months after the last subject enrolled. TTR is defined as the time from the first administration to the subjects' first CR, CRi, or PR.
Duration of Response (DOR) Up to 9 months after the last subject enrolled. DOR is defined as the time from the subject's first CR, CRi, or PR to PD or death from any cause.
the time of half absolute lymphocyte value (ALC) Up to 9 months after the last subject enrolled. The time of half absolute lymphocyte value (ALC) is defined as the time from the first administration to 50% reduction of ALC of baseline.
Adverse events Up to 9 months after the last subject enrolled. Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Trial Locations
- Locations (11)
The First Affilated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The First Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hanzhou, Zhejiang, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Zhujiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Hainan General Hospital
🇨🇳Haikou, Hainan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital medical college Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
People's hospital of Jiangsu Province
🇨🇳Suzhou, Jiangsu, China
The First Affilated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Institute of blood transfusion of Chinese Academy of Medical Sciences
🇨🇳Tianjin, Tianjin, China