Global Trial in APG2575 for Patients With CLL/SLL

A Global Multicenter, Open Label, Randomized Phase 3 Registrational Study of Lisaftoclax (APG-2575) in Previously Treated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (GLORA Study)

This is a global multicenter, open label, randomized, registrational phase III study to investigate the efficacy and safety of lisaftoclax in combination with BTK inhibitors in CLL/SLL patients who previously treated with BTK inhibitors

Study Overview

• Status: Recruiting
• Conditions: CLL/SLL
• Intervention / Treatment: Drug: lisaftoclax +BTK inhibitor; Drug: BTK inhibitor

Detailed Description

Approximately 440 patients will be enrolled, the patients who meet the eligibility criteria will be randomized in a 1:1 ratio to investigational arm (lisaftoclax in combination with a BTK inhibitor) or the control arm (BTK inhibitor alone). These patients with CLL/SLL have been on BTKi monotherapy and meet all other protocol required eligibility criteria.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Laura Glass, MD; Phone Number: 301-520-5964; Email: laura.glass@ascentage.com
• Study Contact Backup: Name: Yifan Zhai, MD; Phone Number: 301-549-6188; Email: yzhai@ascentage.com

Study Locations

• Russian Federation
  • Kaluga, Russian Federation, 246007
    • Recruiting
    • Kaluga Regional Clinical Research
    • Principal Investigator: Elena Borisenkova, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. - Age ≥ 18 years.
2. . Patients that have documented CLL/SLL who meet iwCLL 2018 criteria for CLL treatment guidelines are eligible for treatment and must be receiving BTKi monotherapy for at least 12 months
3. ECOG Performance Status grade 0-2

4. Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of screening initiation as follows:

   • Absolute neutrophil count ≥ 1.0 × 109/L
   • Platelet counts ≥ 75 × 109/L; in cases of thrombocytopenia
   • Total hemoglobin ≥ 9 g/dL,

5. Adequate renal function

   • Creatinine clearance must be > 50 ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x actual body weight)/(72 x creatinine), for women x 0.85) or an equally accurate method.
   • For patients with creatinine values within the normal range, the calculation of clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 50 ml/min may be eligible if a repeat estimate after adequate hydration is > 50 ml/min.

6. Adequate liver function as indicated by:

   • Total bilirubin ≤ 1.5 x ULN, except patients with known Gilbert's Syndrome
   • Aspartate aminotransferase (AST) ≤ 2.5 x the institutional ULN value
   • Alanine aminotransferase (ALT) ≤ 2.5 x the institutional ULN value,
   • International normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT) ≤ 1.5×ULN.
7. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

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
Active Comparator: Arm 1; Combination therapy	Drug: lisaftoclax +BTK inhibitor; lisaftolax + BTK inhibitor
Active Comparator: Arm 2; mono therapy	Drug: BTK inhibitor; BTK inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	To evaluate the progression-free survival (PFS) of lisaftoclax in combination with BTKi compared with BTKi monotherapy in CLL/SLL patients previously treated with BTKi as determined by independent radiological review committee (IRC) using the iwCLL guidelines	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	To evaluate overall survival (OS) of lisaftoclax in combination with BTKi versus BTKi	12 months

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): October 20, 2025
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 26, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: APG2575CG301

Drug and device information, study documents

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