APG-2575 treatment for 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

This study is testing a new treatment called APG-2575, both alone and with other medications, to see how well it works for people with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 123 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, rituximab, ibrutinib
• Locations: 18 sites (Beijing, Beijing Municipality and 17 other locations)
• Trial ID: NCT04494503 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of APG-2575, both as a standalone treatment and in combination with rituximab or ibrutinib, for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It consists of two main parts: the first part focuses on the single-agent use of APG-2575 at varying doses, while the second part examines its combination with other therapies through a structured dose escalation and expansion approach. The study aims to determine the maximum tolerated dose and the recommended phase 2 dose for each combination treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory CLL/SLL who meet specific health criteria.

Not a fit: Patients with other types of leukemia or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat CLL/SLL.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in CLL/SLL, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

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

1. Age ≥18 years old.
2. Diagnosis as relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma according to the IWCLL NCI-WG guidelines revised in 2008.
3. Through radiological assessment, subjects with a lymph node length ≥ 10 cm require prior approval from the sponsor before enrollment.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1.
5. QTcF interval ≤450ms in males, and ≤470ms in females.
6. Adequate bone marrow function independent of growth factor and transfusion.
7. Adequate renal and liver function.
8. 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.
9. 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.
10. Male subjects must avoid sperm donation throughout the treatment period and for at least three months following the last dose of study drug.
11. 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).
12. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

Patients 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 within 24 months or autologous hematopoietic stem cell transplantation within 12 months.
2. Monoclonal antibody therapy against CLL was adopted within 4 weeks prior to the first dose of the study drug.
3. 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.
4. 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.
5. 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.
6. Received Bcl-2 inhibitor treatment.
7. Invasive NHL transformation or central nervous system (CNS) involvement. has occurred.
8. Cardiovascular disease of grade ≥2 (New York Heart Association Class).
9. 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.
10. Warfarin or other anticoagulants is required.
11. Known to be allergic to study drug ingredients or their analogues.
12. Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment.
13. 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;
    * confinement and resection of previously cured malignancies (or other treatment).
14. Has malabsorption syndrome or other conditions that are not suitable for enteral administration.
15. Uncontrolled other clinically significant symptoms, including but not limited to: uncontrolled systemic infections (viruses, bacteria, or fungi), including but not limited to known hepatitis B virus (HBV) surface antigens and DNA positive(HBV-DNA≥2000copies/mL or ≥500IU/mL); Hepatitis C virus (HCV) antibody positive or RNA positive; human immunodeficiency virus (HIV) antibody positive; Febrile neutropenia occured within 1 week before administration.
16. 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).
17. Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for participation in the study.

Where this trial is running

Beijing, Beijing Municipality and 17 other locations

• Peking University Third Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Chongqing Cancer Hospital — Chongqing, Chongqing Municipality, China (RECRUITING)
• Nanfang Hospital of Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
• Guangxi Medical University Affiliated Tumor Hospital — Nanning, Guangxi, China (RECRUITING)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (RECRUITING)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (RECRUITING)
• Henan Provincial Oncology Hospital — Zhenzhou, Henan, China (RECRUITING)
• Union Hospital medical college Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)
• Xiangya Hospital Central South University — Changsha, Hunan, China (RECRUITING)
• The First Affiliated Hospital of Nanjing Medical University — Nanjing, Jiangsu, China (RECRUITING)
• Zhongda Hospital Southeast University — Nanjing, Jiangsu, China (RECRUITING)
• The First affiliated hospital of Soochow University — Suzhou, Jiangsu, China (RECRUITING)
• The First affiliated hospital of Nanchang University — Nanchang, Jiangxi, China (RECRUITING)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (RECRUITING)
• Fudan University Zhongshan Hospital — Shanghai, Shanghai Municipality, China (NOT_YET_RECRUITING)
• Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (RECRUITING)
• The First Bethune Hospital of Jilin University — Hangzhou, Zhejiang, China (RECRUITING)
• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Jianyong Li, M.D.

Conditions: Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, APG-2575, rituximab, ibrutinib, chronic lymphocytic leukemia, small lymphocytic lymphoma