A Global Study of Lisaftoclax (APG-2575) Combined With Acalabrutinib Versus Immunochemotherapy for Newly Diagnosed CLL/SLL.

CLL/SLL Clinical Trial

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06319456
• Other study ID #: APG2575CC301
• Status: Recruiting
• Phase: Phase 3
• Start date: April 7, 2024
• Est. completion date: August 2028

Study information

• Verified date: May 2024
• Source: Ascentage Pharma Group Inc.
• Contact: Yifan Zhai, M.D., Ph.D.
• Phone: +86-20-28068501
• Email: yzhai[@]ascentage.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 344
• Est. completion date: August 2028
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• CLL/SLL

Intervention

Drug:
• Lisaftoclax (APG-2575)
QD, oral administration, every 28 days for a dosing cycle.
• Acalabrutinib
BID, oral administration, every 28 days for a dosing cycle.
• Fludarabine
Every 28 days for a treatment cycle, administration of 6 cycles.
• Cyclophosphamide,CTX
Every 28 days for a treatment cycle, administration of 6 cycles.
• Rituximab
Every 28 days for a treatment cycle, administration of 6 cycles.
• Chlorambucil
Every 28 days for a treatment cycle, administration of 6 cycles.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Hematology Hospital of the Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Provincial Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Ascentage Pharma Group Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progress Free Survival (PFS)	PFS is defined as the time from randomization to disease progression(PD) or death from any cause.	Up to 1 year
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of patients who have achieved CR, CRi or PR.	Up to 1 year
Secondary	Minimal Residual Disease (MRD) negativity rate	To observe the proportion of patients with MRD negativity in bone marrow, peripheral blood, either or both.	Up to 1 year
Secondary	Safety evaluation based on the adverse event concurrence	Number of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.	Up to 1 year