Global Trial in APG2575 for Patients With CLL/SLL

Study Overview
=================
Brief Summary
-----------------
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

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.

Official Title
-----------------
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)

Conditions
-----------------
CLL/SLL

Intervention / Treatment
-----------------
* Drug: lisaftoclax +BTK inhibitor
* Drug: BTK inhibitor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Age ≥ 18 years. . 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 ECOG Performance Status grade 0-2 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, 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. 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. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 ratio to investigational arm (lisaftoclax in combination with BTKi ) or the control arm (BTKi).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Combination therapy | Drug: lisaftoclax +BTK inhibitor<br>* lisaftolax + BTK inhibitor<br>|
| Active Comparator: Arm 2<br>mono therapy | Drug: BTK inhibitor<br>* BTK inhibitor<br>|

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 |