A study testing the new drug Lisaftoclax for newly diagnosed acute myeloid leukemia(GLORA-3)
- Conditions
- Acute myeloid leukemia
- Interventions
- Registration Number
- 2024-516436-10-00
- Lead Sponsor
- Ascentage Pharma Group Inc.
- Brief Summary
To assess the efficacy of APG-2575 combined with AZA versus placebo combined with AZA in the treatment of patients with newly diagnosed AML who are elderly or ineligible for standard induction chemotherapy (cytarabine and anthracyclines).
- Detailed Description
The newly diagnosed acute myeloid leukemia, who are not eligible for standard induction chemotherapy, will be randomized to the investigational group (Lisaftoclax+ AZA) or the control group (placebo+ AZA).
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 16
Age ≥18 years.
Patient who is able to understand and voluntarily sign the written informed consent form before any study-specified procedures.
Patient must be willing and able to complete study procedures and follow-up examinations.
Patient must be newly diagnosed with de novo AML based on WHO 2022 Acute Myeloid Leukemia (AML) criteria, and be ineligible for standard chemotherapy (cytarabine and anthracyclines) due to the age or concomitant illness. Elderly AML patient/AML patient intolerant to standard chemotherapy are defined as follows: (1) Age ≥ 70 years or (2) Age ≥ 18 years and < 70 years, and they must meet at least one of the following criteria: • ECOG Performance Status score of 2-3; • Cardiac history of congestive heart failure (CHF) requiring clinical treatment, ejection fraction ≤ 50% or chronic stable angina; • Diffusing capacity of the lungs for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in one second (FEV1) ≤ 65%; (See Section 8.2.5) • 30 mL/min ≤ creatinine clearance < 45 mL/min • 1.5 × ULN < total bilirubin ≤ 3.0 × ULN • Other concomitant illnesses that prevent subjects from receiving standard chemotherapy, at the discretion of the investigator, must be reviewed and approved by the sponsor before study enrollment.
Life expectancy of ≥ 3 months.
Patient who is able to receive oral administration.
Patient aged ≥ 70 years with ECOG score of 0-2, or those aged ≥ 18 years and < 70 years with ECOG score of 0-3.
Creatinine clearance (CCr) must be ≥ 30 mL/min (calculated using Cockcroft–Gault formula).
White blood cell (WBC) count ≤ 30 × 109/L (hydroxycarbamide is allowed to be used to reach this criterion).
Liver function: Both ALT and AST ≤ 2.5 × ULN, and total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 3 × ULN for patients aged ≥ 18 years and < 70 years).
Males and females with childbearing potential (only postmenopausal women who have not menstruated for at least 12 months can be considered infertile) who agree to take effective contraceptive measures as confirmed by the investigator throughout the treatment period and at least 6 months after the last dose of the study drug.
Patient diagnosed with acute promyelocytic leukemia (FAB classification of AML-M3 or WHO classification of APL with PML-RAR α or t (9; 22) (q34.1; q11.2); BCR-ABL1-positive AML patients).
Active leukemic infiltration of the central nervous system.
Active fungal/bacterial/viral infection requiring systemic treatment, including but not limited to HIV antibody positive, HCV antibody or RNA positive, HBsAg positive and HBV-DNA ≥ 2,000 copies/mL (or ≥ 500 IU/mL); those who are suffering from COVID-19 with serious clinical symptoms (subjects who receive injections with COVID-19 vaccine or other live-attenuated vaccines over 28 days before the first dose of the study drug can be enrolled).
Use of moderate and/or strong CYP3A4 inducers and/or inhibitors within 7 days prior to the first dose of the study drug.
Patient who has been previously treated (including chemotherapy, targeted drugs, monoclonal antibodies and investigational drugs, excluding supportive treatments and hydroxycarbamide) for hematologic disorders, such as AML or MDS.
Patient who has a cardiovascular disability status of New York Heart Association (NYHA) Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea or angina pectoris.
Subjects who have malabsorption syndrome or other conditions, making them unable to receive enteral administration or resulting in an impact on drug absorption.
Subjects who have a history of other malignancies before the start of the study, with the exception of: • Cervical carcinoma in situ or breast cancer in situ after adequate treatment; • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; • Previous malignancies that are not spread, surgically resected (or treated by other means) and clinically cured.
Any other condition or circumstance that would, at the discretion of the investigator, make the subject unsuitable for the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Lisaftoclax (APG-2575) combined with Azacitidine Lisaftoclax (APG-2575) - Lisaftoclax (APG-2575) combined with Azacitidine Azacitidine Injection - Placebo combined with Azacitidine Placebo - Placebo combined with Azacitidine Azacitidine Injection -
- Primary Outcome Measures
Name Time Method Overall survival (OS): Interval between the date of randomization to the date of death of any cause. Survival time will be censored at the latest known survival date of the subject if death cannot be confirmed. Overall survival (OS): Interval between the date of randomization to the date of death of any cause. Survival time will be censored at the latest known survival date of the subject if death cannot be confirmed.
- Secondary Outcome Measures
Name Time Method Composite complete response (CRc) rate: The proportion of patients who have achieved CR, CRi and CRh in total analysis population. Composite complete response (CRc) rate: The proportion of patients who have achieved CR, CRi and CRh in total analysis population.
Event-free survival (EFS): The interval from the date of randomization to the time point when any of the following “events” occur (whichever occurs first): • Progressive disease; • Disease recurrence after CR/CRi/CRh/MLFS; • Death of any cause (including but not limited to death caused by leukemia or therapeutic drugs); • CR/CRi/CRh/MLFS is not achieved after at least 6 treatment cycles. Event-free survival (EFS): The interval from the date of randomization to the time point when any of the following “events” occur (whichever occurs first): • Progressive disease; • Disease recurrence after CR/CRi/CRh/MLFS; • Death of any cause (including but not limited to death caused by leukemia or therapeutic drugs); • CR/CRi/CRh/MLFS is not achieved after at least 6 treatment cycles.
Complete response (CR) rate: The proportion of patients with complete response in the total analysis population. Complete response (CR) rate: The proportion of patients with complete response in the total analysis population.
Overall response rate (ORR): The proportion of patients who have achieved CR, CRi, CRh, MLFS and PR in total analysis population. Overall response rate (ORR): The proportion of patients who have achieved CR, CRi, CRh, MLFS and PR in total analysis population.
Time to response (TTR): The interval from the date of randomization to the date of the first CR, CRi, or CRh. Time to response (TTR): The interval from the date of randomization to the date of the first CR, CRi, or CRh.
Duration of response (DOR): The interval from the date of confirming response (CR/CRi/CRh) to the date of disease recurrence or death of any cause (whichever occurs first). DOR will be calculated for patients with the best response of CR, CRh and CRi separately. Duration of response (DOR): The interval from the date of confirming response (CR/CRi/CRh) to the date of disease recurrence or death of any cause (whichever occurs first). DOR will be calculated for patients with the best response of CR, CRh and CRi separately.
Safety and tolerability of subjects: Treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated. Safety and tolerability of subjects: Treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.
Population pharmacokinetic (Pop PK) parameters of APG-2575. Population pharmacokinetic (Pop PK) parameters of APG-2575.
Results of EORTC QLQ C30 (V3) and EuroQol 5-Dimension (EQ-5D) questionnaire. Results of EORTC QLQ C30 (V3) and EuroQol 5-Dimension (EQ-5D) questionnaire.
Trial Locations
- Locations (2)
Azienda Ospedaliero-Universitaria Policlinico Umberto I
🇮🇹Rome, Italy
Humanitas Mirasole S.p.A.
🇮🇹Rozzano, Italy
Azienda Ospedaliero-Universitaria Policlinico Umberto I🇮🇹Rome, ItalyMassimo BrecciaSite contact+390685795440breccia@bce.uniroma1.it