Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: APG-2575 single agent in Relapse/Refractory CLL/SLL APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle. |
Drug: APG2575
APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle.
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Outcome Measures
Primary Outcome Measures
- 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
- 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 Progression (TTP) [Up to 9 months after the last subject enrolled.]
TTP is defined as the time from the first administration to PD.
- 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.
- Overall Survival (OS) [Up to 9 months after the last subject enrolled.]
OS is defined as the time from the first administration to death.
- 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.
- 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.
- 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.
Other Outcome Measures
- Minimal Residual Disease (MRD) negative rate [Up to 9 months after the last subject enrolled.]
To observe the proportion of subjects with MRD negative status in bone marrow, peripheral blood, one or both.
- Bcl-2 expression [Up to 9 months after the last subject enrolled]
Potential biomarkers to be evaluated included the association of Bcl-2 expression with the efficacy of APG-2575 monotherapy.
Eligibility Criteria
Criteria
Inclusion Criteria:
Subjects who meet each of the following inclusion criteria are eligible to participate in this study:
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Age ≥18 years old.
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Pathologically confirmed CLL/SLL according to the 2018 revised IWCLL NCI-WG guidelines, subject with measurable lesions or splenomegaly due to CLL.
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Expected survival is at least 12 weeks.
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Refractory, recurrent, or intolerant to BTK inhibitors and immunochemotherapy,or first-line treatment with BTK inhibitors fails and is not suitable for immunochemotherapy.
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Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2.
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QTcF interval ≤450ms in males, and ≤470ms in females.
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Adequate bone marrow function independent of growth factor and transfusion.
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Adequate renal and liver function.
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Clinically significant adverse reactions related to previous treatments returned to less than grade 2.
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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.
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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.
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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).
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Willingness and ability to comply with study procedures and follow-up examination.
Exclusion Criteria:
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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Use the following drugs within 7 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.
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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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Cardiovascular disease of grade ≥2 (New York Heart Association Class).
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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.
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Warfarin or other anticoagulants is required.
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Known to be allergic to study drug ingredients or their analogues.
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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:
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Fully treated cervical carcinoma in situ;
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Completely resected basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
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Confinement and resection of previously cured malignancies (or other treatment).
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Has malabsorption syndrome or other conditions that are not suitable for enteral administration.
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Uncontrolled other clinically significant symptoms, including but not limited to: uncontrolled systemic infections (viruses, bacteria, or fungi), including but not limited to active hepatitis B (non-active hepatitis B subjects with HBV-SURFACE antigen positive but HBV-DNA≤2,000 copies/mL or 500 IU/ mL can be enrolled) ; Hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; Febrile neutropenia occured within 1 week before administration.
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Primary active autoimmune diseases and connective tissue diseases, such as active and uncontrolled primary autoimmune hemocytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP).
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The First Affilated Hospital of Bengbu Medical University | Bengbu | Anhui | China | 233099 |
2 | Anhui Provincial Hospital | Hefei | Anhui | China | 230002 |
3 | Beijing Chao-yang Hospital of Capital Medical University | Beijing | Beijing | China | 100020 |
4 | The First Hospital of Peking University | Beijing | Beijing | China | 100034 |
5 | Beijing Friendship Hospital of Capital Medical University | Beijing | Beijing | China | 100050 |
6 | The Third Hospital of Peking University | Beijing | Beijing | China | 100191 |
7 | The fifth medical center of PLA General Hospital | Beijing | Beijing | China | 222002 |
8 | Peking Union Hospital of Chinese Academy of Medical Sciences | Beijing | Beijing | China | |
9 | Peking Union Hospital of Chinese Academy of Medical Sciences | Beijing | Bejing | China | 215127 |
10 | Chongqing University Cancer Hospital | Chongqing | Chongqing | China | 400030 |
11 | Southwest Hospital of Army Medical University | Chongqing | Chongqing | China | 671014 |
12 | Quanzhou First Hospital of Fujian Province | Quanzhou | Fujian | China | 362002 |
13 | The First Affiliated Hospital of Xiamen University | Xiamen | Fujian | China | 361003 |
14 | Lanzhou University Second Hospital | Lanzhou | Gansu | China | 730030 |
15 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
16 | Guangdong Province People's Hospital | Guangzhou | Guangdong | China | 510080 |
17 | Zhujiang Hospital of Southern Medical University | Guangzhou | Guangdong | China | 510280 |
18 | Nanfang Hospital of Southern Medical University | Guangzhou | Guangdong | China | 510515 |
19 | Shenzhen Second People's Hospital | Shenzhen | Guangdong | China | 518025 |
20 | Guangxi Tumour Hospital | Nanning | Guangxi | China | 530021 |
21 | The First Affilated Hospital of Guizhou Medical University | Guiyang | Guizhou | China | 550004 |
22 | Hainan General Hospital | Haikou | Hainan | China | 570311 |
23 | The First Affilated Hospital of Haerbing Medical University | Haerbin | Heilongjiang | China | 150007 |
24 | Henan Cancer Hospital | Zhengzhou | Henan | China | 450003 |
25 | Henan Province People's Hospital | Zhengzhou | Henan | China | 450003 |
26 | The first Affiliated Hospital of Henan Secience and Technology University | Zhengzhou | Henan | China | 450052 |
27 | Union Hospital medical college Huazhong University of Science and Technology | Wuhan | Hubei | China | 430022 |
28 | The First Hospital of Yichang | Yichang | Hubei | China | 443099 |
29 | Hunan Cancer Hospital | Changsha | Hunan | China | 410031 |
30 | Zhongda Hospital of Southeast University | Nanjing | Jiangsu | China | 215558 |
31 | The First Affilated Hospital of Soochow University | Suzhou | Jiangsu | China | 215006 |
32 | People's hospital of Jiangsu Province | Suzhou | Jiangsu | China | |
33 | Wuxi people's Hospital | Wuxi | Jiangsu | China | 214023 |
34 | The affilated Hospital of Xuzhou Medical University | Xuzhou | Jiangsu | China | 221004 |
35 | The affiliated Hospital of Xuzhou Medical University | Xuzhou | Jiangsu | China | 221004 |
36 | The First Affilated Hospital of Nanchang University | Nanchang | Jiangxi | China | 330006 |
37 | The First Bethune Hospital of Jiling University | Changchun | Jilin | China | 130061 |
38 | The Second Hospital of Dalian Medical University | Dalian | Liaoning | China | 116023 |
39 | The Affiliated Hospital of Inner Mongolia Medical University | Hohhot | Neimengol | China | 750306 |
40 | Binzhou Medical University Hospital | Binzhou | Shandong | China | 256699 |
41 | Qilu Hospital of Shandong University | Jinan | Shandong | China | 250063 |
42 | Linyi Cancer Hospital | Linyi | Shandong | China | 276002 |
43 | The affilated Hospital of Qingdao University | Qingdao | Shandong | China | 266003 |
44 | Tongji Hospital of Tongji University | Shanghai | Shanghai | China | 200065 |
45 | Xi'an International Medical Center Hospital | Xi'an | Shanxi | China | 710100 |
46 | West China Hospital of Sichuan University | Chengdu | Sichuan | China | 610044 |
47 | Sichuan Province People's Hospital | Chengdu | Sichuan | China | 610072 |
48 | Institute of blood transfusion of Chinese Academy of Medical Sciences | Tianjin | Tianjin | China | 215127 |
49 | Tianjing Medical University General Hospital | Tianjin | Tianjin | China | 300052 |
50 | The First Affilated Hospital of Xinjiang Medical University | Urumqi | Xinjiang | China | 830011 |
51 | Xinjiang Uiger Municipal People's Hospital | Ürümqi | Xinjiang | China | 830001 |
52 | The Second Affilated Hospital of Zhejiang University School of Medicine | Hangzhou | Zhejiang | China | 310003 |
53 | The First Affiliated Hospital of Zhejiang University School of Medicine | Hanzhou | Zhejiang | China | 310003 |
Sponsors and Collaborators
- Ascentage Pharma Group Inc.
Investigators
- Study Director: Yifan Zhai, MD, PhD, Ascentage Pharma Group Inc.
- Principal Investigator: Jianyong Li, M.D., The First Affiliated Hospital with Nanjing Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APG2575CC201