2023-508005-24-00
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/Small Lymphocytic Lymphoma (GLORA Study)
概览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 232
- 试验地点
- 72
- 主要终点
- PFS assessed by IRC defined as the time from randomization to the first occurrence of progression or relapse using the iwCLL guidelines (Hallek Metal 2018) or death from any cause, whichever occurs first.
概览
简要总结
To evaluate the progression-free survival (PFS) of lisaftoclax in combination with a BTKi compared with BTKi monotherapy in CLL/SLL patients previously treated with a BTKi, as determined by independent radiological review committee (IRC) using the iwCLL guidelines (Hallek M et al 2018).
研究设计
- 分配方式
- Randomized
- 主要目的
- A Global Multicenter, Open Label, Randomized Phase 3 Registrational Study Of Lisaftoclax (apg-2575)
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Aged ≥ 18 years.
- •Patients that have documented CLL/SLL who meet iwCLL 2018 criteria for CLL treatment guidelines are eligible. • 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 ≥ 2.5 cm, • ALC ≥ 25x 109 /L • Have ≥ 1 high-risk factor(s) (del17p/p53mut, unmutated IGHV, complex karyotype ≥ 5 factors (≥ 3 chromosomal abnormalities and ≥ 1 biological/structural aberrations).
- •ECOG performance status 0-
- •Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of randomization 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 bodyweight) / (72 x creatinine), for women x
- •or an equally accurate method.
- •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.
排除标准
- •Achieved complete response (CR) or CRi status or disease progression while on BTKi (acalabrutinib, ibrutinib, zanubrutinib) monotherapy prior to study entry.
- •Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ grade 1 or baseline, except alopecia or neuropathy.
- •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.
- •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).
- •Underlying clinically significant cardiovascular disease such as: symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening or any cardiovascular disability status of New York Heart Association Class ≥
- •Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
- •Uncontrolled medical condition (e.g., diabetes).
- •Known to have central nervous system (CNS) involvement.
- •Prior malignancy within 2 years of treatment that required radiotherapy, or systemic therapy.
- •Patients treated with strong CYP3A4 inhibitors/inducers (patients can be washed out allowing 5 half-lives prior to study treatment and/or switched to non-prohibited drug.
结局指标
主要结局
PFS assessed by IRC defined as the time from randomization to the first occurrence of progression or relapse using the iwCLL guidelines (Hallek Metal 2018) or death from any cause, whichever occurs first.
PFS assessed by IRC defined as the time from randomization to the first occurrence of progression or relapse using the iwCLL guidelines (Hallek Metal 2018) or death from any cause, whichever occurs first.
次要结局
- Key secondary endpoint: Overall survival (OS) defined as the time from randomization to the time of death from any cause.
- Other secondary efficacy endpoints: PFS assessed by investigator is defined as the time from randomization to the first occurrence of progression or relapse using the iwCLL guidelines (Hallek Metal 2018) or death from any cause, whichever occurs first.
- Other secondary efficacy endpoints: Overall response rate (ORR) is defined as the proportion of patients with complete response (CR), complete response with incomplete recovery (CRi) and partial repose (PR).
- Other secondary efficacy endpoints: Proportion of patients with CR/CRi.
- Other secondary efficacy endpoints: Duration of Response.
- Other secondary efficacy endpoints: Proportion of patients with undetectable minimal residual disease.
- Safety endpoints: Incidence and severity of adverse events, serious adverse events and changes in laboratory results, including hematology and biochemistry, during and within 30 days of treatment discontinuation.
- Safety endpoints: Incidence of adverse events of interest, including atrial fibrillation and tumor lysis syndrome.
- Pharmacokinetics endpoint: Population PK analysis.
- Patient-Reported Outcome (PRO) Measures endpoint: The PRO outcome measures will evaluate the European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire Core-30 (QLQ-C30) and associated CLL module (QLQ-CLL17).
- Health Economics and Outcomes Research (HEOR) endpoint: A EuroQoL5-Dimension (EQ-5D-5L) questionnaire will be used
研究者
Yifan Zhai, M.D., Ph.D.
Scientific
Ascentage Pharma Group Inc.
研究点 (72)
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