Combining APG-2575 with Azacitidine for treating Acute Myeloid Leukemia

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)

This study is testing if a new treatment combining APG-2575 with azacitidine can help people with newly diagnosed acute myeloid leukemia who can't have standard chemotherapy feel better compared to a placebo with azacitidine.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 486 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 6 sites (Tianjin, Tianjin Municipality and 5 other locations)
• Trial ID: NCT06389292 on ClinicalTrials.gov

What this trial studies

This pivotal phase III study evaluates the efficacy of APG-2575 (Lisaftoclax) in combination with azacitidine compared to a placebo with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for standard chemotherapy. Participants will be randomly assigned to receive either the investigational treatment or the control. The study aims to determine if this combination can improve outcomes for patients who have limited treatment options due to their condition.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with newly diagnosed AML who are ineligible for standard induction chemotherapy.

Not a fit: Patients with acute promyelocytic leukemia or those with active infections requiring systemic treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with acute myeloid leukemia who cannot undergo standard chemotherapy.

How similar studies have performed: Other studies have shown promise in combining novel agents with azacitidine for AML, but this specific combination is being evaluated for the first time in this context.

Eligibility criteria

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 is uncontrolled and requires systemic treatment.
4. Use of strong inducers of CYP3A4 within 7 days prior to the first dose of the investigational drug, and/or use of moderate to strong inhibitors of CYP3A4 within 7 days or 3-5 half-lives (whichever is longer) prior to the first dose of the investigational 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.

Where this trial is running

Tianjin, Tianjin Municipality and 5 other locations

• Hematology Hospital of the Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (Recruiting)
• The First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• Moscow Multidisciplinary Clinical Center "Kommunarka" — Moscow, Russia (Recruiting)
• Botkin Moscow Multidisciplinary Research and Clinical Center — Moscow, Russia (Recruiting)
• Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency — Saint Petersburg, Russia (Recruiting)
• Leningrad Regional Clinical Hospital — Saint Petersburg, Russia (Recruiting)

Study contacts

• Principal investigator: Jianxiang Wang, M.D. — Hematology Hospital of the Chinese Academy of Medical Sciences
• Study coordinator: Yifan Zhai, M.D., Ph.D.

Conditions Acute Myeloid Leukemia; APG -2575; Lisaftoclax