Clinical trial NCT06319456: A Global Study of Lisaftoclax (APG-2575) Combined With Acalabrutinib Versus Immunochemotherapy for Newly Diagnosed CLL/SLL.
Official title: A Global Multicenter, Open Label, Randomized Phase III Confirmatory Study of Lisaftoclax (APG-2575) in Combination With Acalabrutinib Versus Immunochemotherapy in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (GLORA-2).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: CLL/SLL
Keywords: CLL/SLL
Lisaftoclax
APG-2575
Lead sponsor: Ascentage Pharma Group Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-20
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a global, multicenter, randomized, open-label, Phase III confirmatory study to investigate the efficacy and safety of Lisaftoclax (APG-2575) in combination with Acalabrutinib in patients with newly diagnosed CLL/SLL.

Detailed description: The patients with newly diagnosed CLL/SLL, who have met all required eligibility criteria, will be randomized to the investigational group (Lisaftoclax in combination with Acalabrutinib) or the control group (immunochemotherapy, CIT).

Eligibility criteria: 1. CLL/SLL must be diagnosed according to the IWCLL NCI-WG Guidelines (2018 edition) and meet at least one of the criteria requiring treatment.
2. With a measurable disease.
3. ECOG score 0-2.
4. QTcF interval: ≤450ms in males, ≤470ms in females.
5. Adequate bone marrow function independent of growth factor support.
6. Adequate liver, kidney and coagulation function.
7. Males and females of childbearing potential, and their partners voluntarily use effective contraceptive measures throughout the treatment and for at least three months after the last dose of the study drug. Male patients must avoid donation from the first dose of the study drug to three months after the last dose of the study drug.
8. Female patients of childbearing potential have negative serum pregnancy test results within 14 days prior to the first dose of the study drug.
9. Patients must be able to understand and voluntarily sign an informed consent form approved by the Ethics Committee (EC) before commencing any screening or study specific procedures.
10. Must be willing and able to complete research procedures and follow-up examinations.

Exclusion Criteria:

1. Any previous CLL specific treatment.
2. Failure to fully recover adequately from prior surgical procedures at the discretion of the investigator. Patients who receive a major surgery within 28 days prior to the first dose of the study drug or who receive a minor surgery (excluding biopsy) within 14 days prior to the initiation of the study.
3. Presence of significant cardiovascular disease within 6 months prior to study entry.
4. A history of significant kidney, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular, or liver disease, which will have an adverse effect on the patient if he/she participates in the study, at the discretion of the investigator.
5. Patients who require warfarin or other anticoagulants or active hemorrhage occur within 2 months before study entry.
6. Known to have hypersensitivity to the drug ingredient or its analogues.
7. Pregnant or lactating female patients and patients who are expected to become pregnant during the study period or within 3 months after the last dose.
8. Patients who have history of other active malignant tumor other than CLL/SLL within 3 years before study entry.
9. With a malabsorption syndrome or other conditions unsuitable for enteral administration.
10. Other clinically significant uncontrolled symptoms.
11. With primary active autoimmune disease and connective tissue disease.
12. Any other circumstances or conditions that would, at the discretion of the investigator, make the patient unsuitable for the study.

Primary outcomes:
measure: Progress Free Survival (PFS)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 1 year
measure: Minimal Residual Disease (MRD) negativity rate
timeFrame: Up to 1 year
measure: Safety evaluation based on the adverse event concurrence
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Provincial Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Tianjin
country: China
facility: Hematology Hospital of the Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Hematology Hospital of the Chinese Academy of Medical Sciences
name: Lugui Qiu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Province Cancer Hospital
name: Keshu Zhou, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: