CTRI/2026/01/101003招募中3 期
A Global Multicenter, Open Label, Randomized Phase 3 Registrational Study of Lisaftoclax (APG-2575) in Previously Treated Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 440
- 试验地点
- 18
- 主要终点
- 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 guidelines
研究概览
简要总结
This is a global multicenter, open label, randomized pivotal phase 3 study to evaluate efficacy and safety of lisaftoclax in combination with a BTKi in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL or SLL) who were previously treated with a BTKi.
Number of Subjects
Approximately 440 eligible patients with CLL or SLL who have been on a BTKi for at least 12 months as first line, second line or third line of therapy will be randomized in a 1:1 ratio to either the Investigational Arm (lisaftoclax in combination with a BTKi used prior to study entry) or Control Arm (continue on the same BTKi), BTKi includes acalabrutinib, ibrutinib or zanubrutinib.
Lisaftoclax (APG-2575) is administered orally once daily at escalating doses ranging from 20 mg to 400 mg during daily ramp-up, and at 400 mg QD on a continuous basis.
Duration of treatment:
Patients in both the investigational and control arms will be treated until progression, unacceptable toxicity, withdrawal of consent, start of alternate therapy or for administrative reasons deemed necessary by the Sponsor, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •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 ((
- •age) multiply actual body weight)slash(72 into creatinine), for women into 0.85) or an equally accurate method.
排除标准
- •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 Richter’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 patients’ 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. John’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.
- •16 Known to have central nervous system (CNS) involvement.
- •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 study drug within 28 days prior to registration for study screening.
- •21 Vaccination with live vaccines within 14 days prior to screening.
- •(Patients who have received COVID-19 vaccination will be considered as eligible for the study.) 23 Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of study treatment, further pregnancy testing will be performed monthly).
- •24 Fertile men or women of child bearing potential unless, surgically sterile or greater than or equal to 2 years after the onset of menopause or willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index less than 1) and one additional effective (barrier) method during study treatment and for 3 months after the end of study treatment.
结局指标
主要结局
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 guidelines
时间窗: 12 months
次要结局
- To evaluate overall survival (OS) of lisaftoclax in combination with a BTKi versus BTKi monotherapy.(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.)
研究者
研究点 (18)
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