A Global Multicenter, Open Label, Randomized Phase III Confirmatory Study of Lisaftoclax (APG-2575) in Combination with Acalabrutinib versus Immunochemotherapy in Patients with Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (GLORA-2 Study)
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Coagulopatías hemorrágicas, Leucemia linfática crónica y otros SLPC, Leucemia mieloide aguda, Leucemia mieloide crónica, Linfoma, Leucemia
FECHA DE APERTURA
Febrero, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
Age 18 years
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
Patients must be willing and able to complete study procedures and follow-up examinations
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).
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).
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2
QT interval corrected using the Fridericia's formula (QTcF) on electrocardiogram (ECG): QTcF450 ms in males or 470 ms in females
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.
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.
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.
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.
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
Patients must be willing and able to complete study procedures and follow-up examinations
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).
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).
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2
QT interval corrected using the Fridericia's formula (QTcF) on electrocardiogram (ECG): QTcF450 ms in males or 470 ms in females
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.
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.
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.
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.
CRITERIOS DE EXCLUSIÓN
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).
Known to have hypersensitivity to ingredients or analogues of drugs used in the study
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.
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.
Malabsorption syndrome or other conditions not suitable for enteral administration.
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.
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).
Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for the study.
TP53 mutation or del (17p).
Transformation to invasive Non-Hodgkins lymphoma (e.g., Richters transformation, prolymphocytic leukaemia or diffuse large B-cell lymphoma) or leukaemia involving the central nervous system. If Richters transformation is suspected, PET-CT or biopsy should be performed to rule it out.
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.
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.
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
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.
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.
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
Known to have hypersensitivity to ingredients or analogues of drugs used in the study
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.
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.
Malabsorption syndrome or other conditions not suitable for enteral administration.
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.
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).
Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for the study.
TP53 mutation or del (17p).
Transformation to invasive Non-Hodgkins lymphoma (e.g., Richters transformation, prolymphocytic leukaemia or diffuse large B-cell lymphoma) or leukaemia involving the central nervous system. If Richters transformation is suspected, PET-CT or biopsy should be performed to rule it out.
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.
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.
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
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.
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.
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
DESCRIPCIÓN
To evaluate the progressionfree survival (PFS) of Lisaftoclax in combination with acalabrutinib versus immunochemotherapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) determinated by Independent Review Committee (IRC).
PALABRAS CLAVE
chronic leukemia, factor xi, leukemia, lymphocytic, lymphoma, ph + acute lymphoblastic leukemia, small lymphocytic lymphoma
