Health Condition 1: C911- Chronic lymphocytic leukemia of B-cell type
Conditions
Interventions
Intervention1: Lisaftoclax (APG-2575) Plus BTKi: Route of Administration - Oral
Lisaftoclax (APG-2575) is administered orally once daily at escalating doses ranging from 20 mg to 400 mg during daily
Sponsors
Ascentage Pharma Group Inc.
IQVIA RDS INDIA PRIVATE LIMITED
Eligibility
Inclusion criteria
Inclusion criteria: 1 Age 18 years or above 2 Patients that have documented CLL or SLL who meet iwCLL 2018 criteria for CLL treatment guidelines are eligible. A Received a BTKi (acalabrutinib, ibrutinib, or zanubrutinib) monotherapy as 1st, 2nd, or 3rd line therapy for 12 months and have best response as either a or b a Stable disease b PR with any of the following baseline risk factors: Lymph node(s) diameter greater or equal to 2.5 CM ALC greater or equal to 25 into 109 per L Have greater or equal to 1 high risk factor(s) (del17p or p53mut, unmutated IGHV, complex karyotype greater or equal to 5 factors (greater or equal to 3 chromosomal abnormalities and greater or equal to 1 biological or structural aberrations) 3 ECOG Performance Status grade 0 to 2 4 Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of randomization as follows: a Absolute neutrophil count greater or equal to 1.0 into 109 per L b Platelet counts greater or equal to 75 into 109 per L, in cases of thrombocytopenia c Total hemoglobin greater or equal to 9 g per dL 5 Adequate renal function Creatinine clearance must be greater than 50 ml per min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men- GFR approx ((140 - age) multiply actual body weight)slash(72 into creatinine), for women into 0.85) or an equally accurate method.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following exclusion criteria are not to be enrolled in this study. 1 Achieved complete response (CR) or CRi status or disease progression while on BTKi (acalabrutinib, ibrutinib, zanubrutinib) monotherapy prior to study entry. 2 Transformation of CLL to Richterâ??s condition. 3 Prior treatment with venetoclax or other Bcl-2 inhibitors. 4 An individual organ or system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition limiting the ability to receive the study treatment, or any other life threatening illness, medical condition, or organ system dysfunction that, in the investigator´s opinion, could compromise the patientsâ?? safety or interfere with the absorption or metabolism of the study drugs (e.g. inability to swallow tablets or impaired resorption in the gastrointestinal tract). 5 Patients receiving acalabrutinib capsule-based therapy (and not acalabrutinib tablet) who require treatment with proton pump inhibitors (e.g, omeprazole esomeprazole, lansoprazole etc,) at study entry. (Patients receiving proton pump inhibitors who switch to H2 receptors antagonists or antacids are eligible for enrollment). 6 Patients who require or are receiving anticoagulation therapy with warfarin or equivalent vitamin K antagonists within 7 days of first dose of the study drug(s). 7 Patients who are pregnant or breastfeeding. 8 Has received the following within 7 days prior to the first dose of study drug: a Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for antineoplastic intent. b CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin or potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. Johnâ??s wort. 9 Radiation within 14 days of study entry 10 Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to less than or equal to grade 1 or baseline, except alopecia or neuropathy. 11 Failure to recover, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days and minor surgery such as a biopsy within 14 days from first dose of study drug. 12 QTcF interval 480ms or other remarkable abnormality of ECG, including second-degree type II atrioventricular block, third-degree atrioventricular block, or bradycardia (ventricular rate consistently less than 50 beats per minute). 13 Underlying clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening or any 14 Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial. 15 Uncontrolled medical condition (e.g., diabetes). 16 Known to have central nervous system (CNS) involvement. 17 Prior malignancy within 2 years of treatment that required radiotherapy, or systemic therapy. 18 Patients treated with strong CYP3A4 inhibitors or inducers (patients can be washed out allowing 5 half-lives prior to study treatment and or switched to non-prohibited drug). 19 History of stroke or intracranial hemorrhage within 3 months prior to registration for study screening or known bleeding disorders 20 Use of investigational agents which might interfere with the s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the progression-free survival (PFS) of lisaftoclax in combination with a BTKi compared with BTKi monotherapy in CLL or SLL patients previously treated with a BTKi, as determined by independent radiological review committee (IRC) using the iwCLL guidelinesTimepoint: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate overall survival (OS) of lisaftoclax in combination with a BTKi versus BTKi monotherapy.Timepoint: 12 months;Other Secondary Objectives 1 To determine efficacy of lisaftoclax plus a BTKi, compared with BTKi monotherapy by additional outcome measures including PFS by investigators, ORR rate, CR/CRi rate, DoR, uMRD rate. 2 To evaluate safety of lisaftoclax plus a BTKi, versus BTKi monotherapy 3 To characterize the population pharmacokinetics of lisaftoclax 4 To evaluate Patient-Reported Outcome (PRO) measures of lisaftoclax plus a BTKi versus BTKi monotherapy based on EORTC QLQ-C30 5 To evaluate Health Economics Outcomes Research (HEOR) measures of lisaftoclax plus BTKi versus BTKi monoherapy based on Europol 5 Dimension (EQ-5D-5L) Timepoint: 12 months | — |
Countries
Australia, Belgium, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Poland, Romania, Russian Federation, Slovakia, Spain, Turkey, United Kingdom, United States of America
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed