Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL

Sponsor
Ascentage Pharma Group Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05147467
Collaborator
(none)
75
53
1
21.7
1.4
0.1

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
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

Study Type:
Interventional
Anticipated Enrollment :
75 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Single-arm, Pivotal Registration Phase II Study of the Efficacy and Safety of APG-2575 Monotherapy in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Actual Study Start Date :
Mar 10, 2022
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Overall Survival (OS) [Up to 9 months after the last subject enrolled.]

    OS is defined as the time from the first administration to death.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  1. 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.

  2. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

Subjects who meet each of the following inclusion criteria are eligible to participate in this study:

  1. Age ≥18 years old.

  2. Pathologically confirmed CLL/SLL according to the 2018 revised IWCLL NCI-WG guidelines, subject with measurable lesions or splenomegaly due to CLL.

  3. Expected survival is at least 12 weeks.

  4. Refractory, recurrent, or intolerant to BTK inhibitors and immunochemotherapy,or first-line treatment with BTK inhibitors fails and is not suitable for immunochemotherapy.

  5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2.

  6. QTcF interval ≤450ms in males, and ≤470ms in females.

  7. Adequate bone marrow function independent of growth factor and transfusion.

  8. Adequate renal and liver function.

  9. Clinically significant adverse reactions related to previous treatments returned to less than grade 2.

  10. 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.

  11. 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.

  12. 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).

  13. 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:

  1. Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cell immunotherapy or autologous hematopoietic stem cell transplantation within 24 months.

  2. 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.

  3. 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.

  4. Received Bcl-2 inhibitor treatment.

  5. Invasive NHL transformation or central nervous system (CNS) involvement has occurred.

  6. Cardiovascular disease of grade ≥2 (New York Heart Association Class).

  7. 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.

  8. Warfarin or other anticoagulants is required.

  9. Known to be allergic to study drug ingredients or their analogues.

  10. Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment.

  11. 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).

  1. Has malabsorption syndrome or other conditions that are not suitable for enteral administration.

  2. 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.

  3. 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).

  4. 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
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.
Responsible Party:
Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier:
NCT05147467
Other Study ID Numbers:
  • APG2575CC201
First Posted:
Dec 7, 2021
Last Update Posted:
Aug 19, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ascentage Pharma Group Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 19, 2022