A clinical trial to study the effect and safety of an intervention drug in elderly participants with newly diagnosed acute myeloid leukemia
Scientific Title of Study
A global, multicenter, randomized, double-blind, phase 3 pivotal registrational clinical study of APG-2575 (Lisaftoclax) combined with azacitidine in elderly patients with newly diagnosed acute myeloid leukemia (GLORA-3)
Trial Acronym
GLORA-3
Secondary IDs if Any
Secondary ID
Identifier
2024-516436-10
Other
APG2575AG301 V1.2 (EU) dated 16 Apr, 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
B block, 1st floor, Old HR Annex Building Apollo Research and Innovations Dept.154/11, Opp,I.I.M., Bannerghatta Road, Bangalore - 560076 Bangalore KARNATAKA
91 9880372464
vishsathya@gmail.com
Dr Punit Jain
Apollo Hospitals Enterprise Limited
, Plot No. 13, Parsik Hill Road, Off Uran Road, Sector - 23, CBD Belapur, Navi Mumbai-400614 Mumbai MAHARASHTRA
91-9553077700
drloki2002@yahoo.com
Dr Anupam Chakrapani
Apollo Multispeciality Hospitals Limited
Clinical Trial and Research Department
Day Care Building, 6th Floor, Back Side,
58, Canal Circular Road, Kolkata-700 054
Kolkata WEST BENGAL
91-9007756054
anupamhemat@gmail.com
Dr T Deenadayalan
Apollo Speciality Hospital
Room number 41, C-Block, Ground Floor, Oncology OPD, Apollo Speciality Hospital
Lake View Road, K. K. Nagar, Madurai-625020
Madurai TAMIL NADU
0452-2581154
drdeena2020@gmail.com
Dr Nataraj K S
Healthcare Global Enterprise Limited
#8, HCG Towers, P. Kalinga Rao Road, Sampangi Rama Nagar, Bengaluru, Karnataka- 560027, India Bangalore KARNATAKA
91-9482141773
drnataraj.ks@hcge1.com
Dr Ajay Gupta
Indraprastha Apollo Hospitals
Sarita Vihar, Delhi-Mathura Road, New Delhi - 110076 New Delhi DELHI
91 7838013018
oncol@rediffmail.com
Dr Ranjit Kumar Sahoo
Institute Rotary Cancer Hospital, All India Institute of Medical Sciences
Room No. 218, 2nd Floor, Department of Medical Oncology, IRCH Building, Ansari Nagar New Delhi-110029
New Delhi DELHI
91-9013956187
drranjitmd@gmail.com
Dr Smita Kayal
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)
Department of Oncology, Service Floor, Saket (East Block) – A Unit of Devki Devi Foundation, 2, Press Enclave Road, Saket, New Delhi-110017
New Delhi DELHI
91-9818548149
atulSharma@maxhealthcare.com
Dr Nitin Sood
Medanta -The Medicity Cancer Institute
Room no.17, 10th Floor, Medanta Cancer Institute, Medanta- The Medicity, Sector 38, Gurugram - 122001 Gurgaon HARYANA
91-9769132085
punitjn@gmail.com
Dr Akash Kumar
National Cancer Institute, All India Institute of Medical Sciences
Room no - 203, 2nd Floor,
Research Block, National Cancer Institute,
AIIMS Jhajjar Campus, Vill Badsa,
Haryana-124105
Jhajjar HARYANA
91-9910850134
akashjha08@yahoo.com
Dr Prakas Kumar Mandal
NRS Medical College and Hospital
Haematology Department, Centenary Building, 4th Floor , Nil Ratan Sircar Medical College and Hospital, 138-A.J.C. Bose Road Kolkata-700014 Kolkata WEST BENGAL
91 9868764808
prakas70@gmail.com
Dr Narendra Agrawal
Rajiv Gandhi Cancer Institute & Research Centre
Sector 5, Rohini, New Delhi, 110085 New Delhi DELHI
91 9868764808
narendra_agl@rediffmail.com
Dr Anant Gokarn
Tata Memorial Centre Advanced Centre for Treatment
Room no 103/307, AHL & BMT OPD, 1st and 3rd floor, shanti sadan building Department of Medical Oncology Owe camp, Sector 22, ACTREC Advanced Centre for Training Research and Education in Cancer, Kharghar, Navi Mumbai Raigarh-410210 Mumbai MAHARASHTRA
Lisaftoclax (APG-2575) in combination with Azacitidine
Lisaftoclax (APG-2575): QD, oral administration, every 28 days for a dosing cycle.
Azacitidine Injection: QD, subcutaneous or intravenous injection, D1-7 or D1-5 and 8-9 in 28-day cycle.
Comparator Agent
Placebo combined with Azacitidine
Placebo: QD, oral administration, every 28 days for a dosing cycle.
Azacitidine Injection: QD, subcutaneous or intravenous injection, D1-7 or D1-5 and 8-9 in 28-day cycle.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Patient will be eligible for the study if they meet each of the following criteria:
1. Age 18 years or more.
2. Patient must be newly diagnosed with de novo AML based on WHO 2022 Acute Myeloid Leukemia (AML) criteria, and be ineligible for standard chemotherapy.
3. Life expectancy of greater than or equal to 3 months.
4. Patient who is able to receive oral administration.
5. Patient aged greater than or equal to 70 years with ECOG score of 0-2, or those aged greater than or equal to 18 years and less than 70 years with ECOG score of 0-3.
6. Creatinine clearance (CCr) must be greater than or equal to 30 mL per min (calculated using Cockcroft–Gault formula. See the Annex)
7. White blood cell (WBC) count less than or equal to 30 into 109 per L (hydroxycarbamide is allowed to be used to reach this criterion)
8. Liver function: Both ALT and AST less than or equal to 2.5 into ULN, and total bilirubin less than or equal to 1.5 into ULN (total bilirubin less than or equal to 3 into ULN for patients aged greater than or equal to 18 years and less than 70 years)
9. 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.
10. Patient who is able to understand and voluntarily sign the written informed consent form before any study-specified procedures
11. Patient must be willing and able to complete study procedures and follow-up examinations
ExclusionCriteria
Details
Patient who meet any of the following exclusion criteria are not eligible for this study:
1. Patient diagnosed with acute promyelocytic leukemia [FAB classification of AML-M3 or WHO classification of acute promyelocytic leukemia (APL) with PML-RAR alpha] or t (9, 22) (q34.1, q11.2), BCR-ABL1-positive AML.
2. Active leukemic infiltration of the central nervous system.
3. Active fungal or bacterial or viral infection requiring systemic treatment.
4. Use of moderate and or strong CYP3A4 inducers and or inhibitors within 7 days prior to the first dose of the study drug.
5. Patient who has been previously treatedfor hematologic disorders, such as AML or myelodysplastic syndrome (MDS).
6. Patient who has a cardiovascular disability status of New York Heart Association (NYHA) Class more than 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.
7. Patient who has malabsorption syndrome or other conditions, making them unable to receive enteral administration or resulting in an impact on drug absorption.
8. Patient who has 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 by other means) and clinically cured.
9. Any other condition or circumstance that would, at the discretion of the investigator, make the subject unsuitable for the study.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Other
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Overall Survival: The primary endpoint was overall survival, defined as the time from the date of randomization to the date of death of any cause.
Upto 5 Years
Secondary Outcome
Outcome
TimePoints
Percentage of Participants with Objective Response Rate (ORR): ORR is defined as the proportion of patients who have achieved CR, CRi, CRh, MLFS or PR.
Up to 5 years
Safety evaluation based on the adverse event concurrence: Number of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) will be evaluated.
Up to 5 years
Target Sample Size
Total Sample Size="486" Sample Size from India="50" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
20/03/2026
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
20/06/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="6" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a global,
multicenter, randomized, double-blind, placebo-controlled, phase 3 pivotal
registrational study, which is designed to assess the overall survival (OS) of
APG-2575 (Lisaftoclax) combined with AZA versus placebo combined with AZA in
patients with newly diagnosed AML who are elderly or ineligible for standard
induction chemotherapy.
Subjects will be
randomized to either of the following two groups in a ratio of 1:1 after
completing screening procedure and being confirmed eligible:
§Investigational
drug group: APG-2575 combined with AZA: APG-2575, oral, once a day (QD) for 28
consecutive days (D1-D28). Azacitidine (AZA) will be administered daily as 75
mg/m2/d by intravenous (IV) infusion or subcutaneously (SC),
ideally, on cycle days 1-7, OR on cycle days 1-5 and 8-9 in a 28-day cycle.
§Control group:
Placebo combined with AZA: placebo, oral, once a day (QD) for 28 consecutive
days (D1-D28). Azacitidine (AZA) will be administered daily as 75 mg/m2/d
by intravenous (IV) infusion or subcutaneously (SC), ideally, on cycle days
1-7, OR on cycle days 1-5 and 8-9in a 28-day cycle.