A 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 vs Immunochemotherapy in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Overview

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).

Interventions

• 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.
• 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.

Primary outcome measures

• Progress Free Survival (PFS) [Time frame: Up to 1 year]

Secondary outcome measures (3)

• Objective Response Rate (ORR) [Time frame: Up to 1 year]
• Minimal Residual Disease (MRD) negativity rate [Time frame: Up to 1 year]
• Safety evaluation based on the adverse event concurrence [Time frame: Up to 1 year]

Eligibility criteria

• CLL/SLL must be diagnosed according to the IWCLL NCI-WG Guidelines (2018 edition) and meet at least one of the criteria requiring treatment.
• With a measurable disease.
• ECOG score 0-2.
• QTcF interval: ≤450ms in males, ≤470ms in females.
• Adequate bone marrow function independent of growth factor support.
• Adequate liver, kidney and coagulation function.
• 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.
• Female patients of childbearing potential have negative serum pregnancy test results within 14 days prior to the first dose of the study drug.
• 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.
• Must be willing and able to complete research procedures and follow-up examinations.

Exclusion criteria

• Any previous CLL specific treatment.
• 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.
• Presence of significant cardiovascular disease within 6 months prior to study entry.
• 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.
• Patients who require warfarin or other anticoagulants or active hemorrhage occur within 2 months before study entry.
• Known to have hypersensitivity to the drug ingredient or its analogues.
• 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.
• Patients who have history of other active malignant tumor other than CLL/SLL within 3 years before study entry.
• With a malabsorption syndrome or other conditions unsuitable for enteral administration.
• Other clinically significant uncontrolled symptoms.
• With primary active autoimmune disease and connective tissue disease.
• Any other circumstances or conditions that would, at the discretion of the investigator, make the patient unsuitable for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 10 centers

• The First Affiliated Hospital of Bengbu Medical College — Bengbu
• Guangdong Provincial People's Hospital — Guangzhou
• Nanfang Hospital of Southern Medical University — Guangzhou
• The affiliated Hospital of Guangdong Medical University — Zhanjiang
• Henan Provincial Cancer Hospital — Zhengzhou
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• Hunan Cancer Hospital — Changsha
• The Second Xiangya Hospital of Center South University — Changsha
• … and 2 more centers

Identifiers

NCT: NCT06319456 · APG2575CC301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗