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

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).

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.

Study Overview

• Status: Recruiting
• Conditions: CLL/SLL
• Intervention / Treatment: Drug: Lisaftoclax (APG-2575); Drug: Acalabrutinib; Drug: Fludarabine; Drug: Cyclophosphamide，CTX; Drug: Rituximab; Drug: Chlorambucil

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).

• Study Type: Interventional
• Enrollment (Estimated): 344
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yifan Zhai, M.D., Ph.D.; Phone Number: +86-20-28068501; Email: yzhai@ascentage.com
• Study Contact Backup: Name: Bo Huang, M.D.; Email: Bo.Huang@ascentage.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • Not yet recruiting
      • The First Affiliated Hospital Of Bengbu Medical College
      • Contact: Yinghua Geng, M.D., Ph.D.
      • Principal Investigator: Yinghua Geng, M.D., Ph.D.
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Not yet recruiting
      • Nanfang Hospital of Southern Medical University
      • Contact: Xutao Guo, M.D., Ph.D.
      • Principal Investigator: Xutao Guo, M.D., Ph.D.
    • Guangzhou, Guangdong, China, 510080
      • Not yet recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Wenyu Li, M.D., Ph.D.
      • Principal Investigator: Wenyu Li, M.D., Ph.D.
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Provincial Cancer Hospital
      • Contact: Keshu Zhou, M.D., Ph.D.; Phone Number: 13674902391; Email: drzhouks77@163.com
      • Principal Investigator: Keshu Zhou, M.D., Ph.D.
  • Hubei
    • Wuhan, Hubei, China, 430023
      • Not yet recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Jun Fang, M.D., Ph.D.
      • Principal Investigator: Jun Fang, M.D., Ph.D.
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Hematology Hospital of the Chinese Academy of Medical Sciences
      • Principal Investigator: Lugui Qiu, M.D., Ph.D.
      • Contact: Lugui Qiu, M.D., Ph.D.; Phone Number: 022-23909272; Email: qiulg@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lisaftoclax (APG-2575) combined with Acalabrutinib	Drug: Lisaftoclax (APG-2575); QD, oral administration, every 28 days for a dosing cycle.; Drug: Acalabrutinib; BID, oral administration, every 28 days for a dosing cycle.
Active Comparator: Immunochemotherapy regimens	Drug: Fludarabine; Every 28 days for a treatment cycle, administration of 6 cycles.; Drug: Cyclophosphamide，CTX; Every 28 days for a treatment cycle, administration of 6 cycles.; Drug: Rituximab; Every 28 days for a treatment cycle, administration of 6 cycles.; Drug: Chlorambucil; Every 28 days for a treatment cycle, administration of 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of patients who have achieved CR, CRi or PR.	Up to 1 year
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
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

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Investigators: Principal Investigator: Lugui Qiu, M.D., Ph.D., Hematology Hospital of the Chinese Academy of Medical Sciences; Principal Investigator: Keshu Zhou, M.D., Ph.D., Henan province Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: APG-2575; CLL/SLL; Lisaftoclax
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Cyclophosphamide; Rituximab; Fludarabine; Acalabrutinib; Chlorambucil
• Other Study ID Numbers: APG2575CC301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No