LISAFTOCLAX for Chronic lymphocytic leukemia | Small lymphocytic lymphoma

Inclusion criteria

• {"criterion_text":"- Age ≥18 years\n- Patients must be able to understand and voluntarily sign a written informed consentthat has been approved by the Ethics Committee (EC) before any screening or study-specific procedure\n- Patients must be willing and able to complete study procedures and follow-up examinations\n- Diagnosed with CLL/SLL based on IWCLL NCI-WG guidelines (2018 Edition) and indicating at least one of the criteria for treatment (see Appendix 14: Treatment Criteria).\n- Measurable disease (peripheral blood lymphocyte ≥ 5 × 109/L, or enlargement of lymph nodes (baseline LDi ≥ 1.5 cm), or hepatomegaly or splenomegaly caused by CLL/SLL).\n- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2\n- QT interval corrected using the Fridericia's formula (QTcF) on electrocardiogram (ECG): QTcF≤450 ms in males or ≤470 ms in females\n- Adequate bone marrow function independent of growth factor support (no growth factor used within 7 days before the first dose of the study drug) and independent of blood transfusion (no whole blood transfusion or blood component transfusion supportive therapy within 7 days before the first dose of the study drug) as follows:  Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (ANC ≥ 0.5 × 109/L specified in patients with bone marrow involvement of CLL/SLL)  Platelet count ≥ 50 × 109/L;  Hemoglobin ≥ 8.0 g/dL.\n- Adequate hepatic, renal, and coagulation functions as follows:  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × Upper Limit of Normal (ULN), serum total bilirubin ≤ 1.5 × ULN;  Serum creatinine ≤ 1.5 × ULN. If serum creatinine > 1.5 × ULN, creatinine clearance (CrCL) must be ≥ 50 mL/min;  International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) ≤ 1.5 × ULN.\n- Males and females of childbearing potential (only postmenopausal women who have not menstruated for at least 12 months or those surgically sterilized can be considered infertile) and their partners voluntarily take effective contraceptive measures throughout the treatment period and at least 3 months after the last dose of the study drug. Male patients must avoid sperm donation from the first dose of the study drug to three months after the last dose of the study drug.\n- Female patients of childbearing potential have negative serum pregnancy test results within approximately 14 days prior to the first dose of the study drug. If the serum pregnancy test results available are > 7 days from the first dose, urine pregnancy test results before the first dose of the study drug must be negative."}

Exclusion criteria

• {"criterion_text":"- Any previous CLL/SLL-specific treatments (excluding corticosteroids for necessary immediate intervention; only a maximum daily equivalent dose of prednisone less than or equal to 20 mg is allowed within 10 days before starting the study treatment).\n- Known to have hypersensitivity to ingredients or analogues of drugs used in the study\n- Pregnant or lactating female patients and patients who are expected to become pregnant during the study period or within 3 months after the last dose.\n- Patients who have history of other active malignant tumor other than CLL/SLL within 3 years before study entry, except for: • Adequately treated carcinoma in situ of cervix uteri • Completely resected basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin • Confinement and resection of previously cured malignancies (or other treatments). Note: If patients stopped antitumor treatment for ≥3 years and there was no tumor recurrence for ≥3 years prior to joining the study, these patients could be enrolled.\n- Malabsorption syndrome or other conditions not suitable for enteral administration.\n- Other clinically significant uncontrolled symptoms, including but not limited to: uncontrolled active systemic infection (virus, bacteria or fungi), known clinically active hepatitis B or C, or HIV infection.\n- Primary active autoimmune and connective tissue diseases, such as active and uncontrolled primary autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP).\n- Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for the study.\n- TP53 mutation or del (17p).\n- Transformation to invasive Non-Hodgkin’s lymphoma (e.g., Richter’s transformation, prolymphocytic leukaemia or diffuse large B-cell lymphoma) or leukaemia involving the central nervous system. If Richter’s transformation is suspected, PET-CT or biopsy should be performed to rule it out.\n- Use of any of the following treatments within 14 days or 5 half-lives before the first dose of the study drug, or clinically significant adverse reactions/toxicities that are related to previous treatments not recovered to < Grade 2: Anti-tumor therapies include chemotherapy, radiotherapy, anti-tumor steroid treatment, anti-tumor Chinese medicine treatment; investigational treatment including targeted small molecule drugs.\n- Use of the moderate to strong CYP3A inhibitors, such as fluconazole, ketoconazole and clarithromycin, within 7 days or 5 half-lives (whichever is shorter) before the first dose of the study drug; or use of strong CYP3A inducers, such as rifampicin, carbamazepine, phenytoin, and St. John's wort, within 14 days before the first dose of the study drug.\n- Failure to fully recover adequately from prior surgical procedures at the discretion of the investigator. Patients who receive a major surgery within 28 days prior to the first dose of the study drug or who receive a minor surgery (excluding biopsy) within 14 days prior to the initiation of the study\n- Presence of significant cardiovascular diseases, such as symptomatic arrhythmia, congestive heart failure, myocardial infarction, or any New York Heart Association (NYHA) grade 3 or 4 cardiovascular disease within 6 months before study entry. Note: Patients with controlled, asymptomatic atrial fibrillation are allowed to participate in this study.\n- A history of significant renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular, or hepatic disease, which will have an adverse effect on the patient if he/she participates in the study, at the discretion of the investigator. Those requiring intervention for any of the above diseases in the past 6 months must be discussed by the investigator and the sponsor.\n- Patients who require warfarin (potential drug-drug interactions may increase exposure to warfarin and related complications) or other anticoagulants or active hemorrhage occur within 2 months before study entry"}

Primary endpoints

• {"endpoint_text":"- IRC-assessed PFS: The time from randomization to PD or death from any cause, whichever occurs first.","definition_or_measurement_approach":"The time from randomization to PD or death from any cause, whichever occurs first (IRC-assessed)."}

Secondary endpoints

• {"endpoint_text":"- Key secondary endpoint: Investigator-assessed PFS: The time from randomization to PD or death from any cause, whichever occurs first.\n- Other secondary endpoints: OS: The time from randomization to death.\n- IRC- and investigator-assessed ORR: ORR includes complete response (CR), complete response with incomplete bone marrow recovery (CRi) or partial response (PR). CLL responsewill be assessed according to IWCLL NCI-WG guidelines (2018 Edition), and SLL response will be assessed according to Lugano 2014 criteria for response assessment in lymphoma.\n- IRC- and investigator-assessed TTR: The interval from randomization to the date of the first confirmed CR, CRi, or PR.\n- IRC- and investigator-assessed DOR: The interval from the date of first confirmed CR, CRi or PR to PD, or the start of a new anti-tumor treatment, or death, whichever occurs first.\n- MRD negativity rate: Proportion of patients with MRD-negative result in bone marrow, peripheral blood, either or both.\n- Safety and tolerability of patients: Treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.\n- Concentration data of Lisaftoclax and critical parameters of population pharmacokinetics.","definition_or_measurement_approach":"Investigator-assessed PFS: time from randomization to PD or death; OS: time from randomization to death; ORR: includes CR, CRi, PR assessed per IWCLL NCI-WG (2018) for CLL and Lugano 2014 for SLL; TTR: interval from randomization to first confirmed CR/CRi/PR; DOR: interval from first confirmed response to PD, new anti-tumor treatment, or death; MRD negativity: proportion with MRD-negative result in bone marrow and/or peripheral blood; Safety: evaluation of TEAEs and TRAEs; Concentration/population PK: measurement of lisaftoclax concentrations and population PK parameters."}

Spain

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

31-07-2025

Processing Time Days

189

Number Of Sites

4

Number Of Participants

10

Czechia

Earliest CTIS Part Ii Submission Date

25-02-2025

Latest Decision Or Authorization Date

29-07-2025

Processing Time Days

154

Number Of Sites

3

Number Of Participants

9

Bulgaria

Earliest CTIS Part Ii Submission Date

27-01-2025

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

403

Number Of Sites

3

Number Of Participants

10

Primary sponsor

Full Name

Ascentage Pharma Group Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"United States","full_name":"Neogenomics Inc.","duties_or_roles":"ROW PD analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"Patient Reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"ROW PD analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"China","full_name":"Calyx China Co. Ltd.","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"China","full_name":"Zhejiang Taimei Medical Technology Co. Ltd.","duties_or_roles":"for distributing SUSAR reports to PIs","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"ROW PD analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"ROW PK/PD kit production","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Resolian Bioanalytics","duties_or_roles":"PK Analysis","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"ClinChoice Medical (TIANJIN) Co., Ltd.","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"Inivata Limited","duties_or_roles":"ROW PD analysis","organisation_type":"Pharmaceutical company"}