A study testing the new drug Lisaftoclax for newly diagnosed acute myeloid leukemia(GLORA-3)

Phase 3

Recruiting

• Conditions: Acute myeloid leukemia
• Interventions: Drug: APG-2575(Lisaftoclax ); Other: Placebo; Drug: Azacitidine Injection

• 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 (APG-2575) + AZA' or the control group 'placebo+ AZA'.

Study Timeline

• Study First Submitted: 2024-04-24
• Study First Submitted QC: 2024-04-26
• Study First Posted: 2024-04-29
• Study Start: 2024-06-11
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-18
• Last Update Posted: 2025-08-22
• Primary Completion: 2028-05-25
• Study Completion: 2029-03-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Patients must have newly diagnosed AML that meets the criteria for acute myeloid leukemia (AML) and ineligible for standard chemotherapy.
2. Life expectancy of ≥3 months.
3. Be able to accept oral administration.
4. Patients aged ≥70 years with ECOG score of 0-2, or those aged≥18 years and <70 years with ECOG score of 0-3.
5. Adequate kidney function.
6. White blood cell ≤ 30×10^9/L.
7. Adequate liver function.
8. Men, women with childbearing potential, and their partners voluntarily use contraception that researchers consider effective.
9. Be able to understand and voluntarily sign written informed consent.
10. Patients must be willing and able to complete study procedures and follow-up examinations.

Exclusion Criteria

1. The patient was diagnosed with acute promyelocytic leukemia or AML BCR-ABL1 positive.
2. Active leukemic infiltration of the central nervous system.
3. Active infection that requires systemic treatment.
4. Use of a moderate or strong inducer and/or inhibitor of CYP3A4 within 7 days prior to first dose of the study drug.
5. Previous treatment for hematologic disorders.
6. Patients who has a cardiovascular disability status of New York Heart Association Class > 2.
7. Patients have malabsorption syndrome or other conditions that cannot be administered through the gastrointestinal tract or affect drug absorption.
8. Patients had a history of other malignancies prior to study initiation.
9. Any other circumstances or conditions, at the discretion of the investigator, make the patient unsuitable to participate in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
APG-2575 (Lisaftoclax) combined with Azacitidine	APG-2575(Lisaftoclax )	-
APG-2575 (Lisaftoclax) 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 (6)

Hematology Hospital of the Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Moscow Multidisciplinary Clinical Center "Kommunarka"; 🇷🇺 Moscow, Russian Federation

Botkin Moscow Multidisciplinary Research and Clinical Center; 🇷🇺 Moscow, Russian Federation

Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency; 🇷🇺 Saint Petersburg, Russian Federation

Leningrad Regional Clinical Hospital; 🇷🇺 Saint Petersburg, Russian Federation