Treatment for patients with relapsed or refractory acute myeloid leukemia

A Phase Ib Study of the Safety, Pharmacokinetic of Lisaftoclax (APG-2575) Single Agent and in Combination With Homoharringtonine or Azacitidine in Patients With Relapsed/Refractory AML

This study is testing a new treatment called APG-2575, both alone and with other drugs, to see if it can help people with relapsed or hard-to-treat acute myeloid leukemia.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 682 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ascentage Pharma Group Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 12 sites (Beijing, Beijing Municipality and 11 other locations)
• Trial ID: NCT04501120 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and pharmacokinetics of APG-2575, both as a single agent and in combination with HHT or AZA, in patients suffering from relapsed or refractory acute myeloid leukemia (AML) and related myeloid malignancies. It consists of three stages: an initial dose-escalation of APG-2575 alone, followed by a dose-escalation of APG-2575 combined with HHT or AZA, and finally an expansion cohort to determine the maximum tolerated dose and recommended phase 2 dose of the combination regimen. The study is open-label and multi-center, allowing for a diverse patient population.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with relapsed or refractory AML or related myeloid malignancies who are ineligible for standard chemotherapy.

Not a fit: Patients with early-stage AML or those who can tolerate standard chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat forms of AML.

How similar studies have performed: Other studies have shown promise with Bcl-2 inhibitors in treating AML, suggesting potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

Subjects who meet each of the following inclusion criteria are eligible to participate in this study:

1. In accordance with the World Health Organization (WHO) 2016 diagnostic criteria for relapsed or refractory acute myeloid leukemia (AML), Mixed phenotype acute leukemia(MPAL), Chronic myelomonocytic leukemia (CMML), Higher-risk myelodysplastic syndrome (HR-MDS) , Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and naïve AML ineligible for treatment with a standard chemotherapy due to age or comorbidities.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2 (0 to 3 for participants \>= 60 to 74 years of age who are evaluated as ineligible for treatment with standard chemotherapy).
3. Subjects can accept oral administration of Lisaftoclax (APG-2575).
4. Life expectancy ≥ 3 months.
5. Adequate renal and liver function.
6. Males, female patients of childbearing potential (postmenopausal women who must have been menopausal for at least 12 months to be considered infertile) and their partners voluntarily take contraception which the investigator considers effective during treatment and at least three months after the last dose of study drug.
7. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).
8. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

Patients who meet any of the following exclusion criteria are not to be enrolled in this study:

1. Patients diagnosed with acute promyelocytic leukemia or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML patients.
2. The persistent toxicities caused by previous chemotherapy or radiotherapy has not been restored to lower than grade 2 by CTCAE 5.0 (except for alopecia).
3. Known leukemia infiltration of the central nervous system.
4. Symptomatic active fungal, bacterial and/or viral infections.
5. Prior history of allogeneic hematopoietic stem cell transplantation or adoptive cell immunotherapy, autologous hematopoietic stem cell transplantation within 12 months.
6. Within 14 days before the first dose of study drug, received chemotherapy (hydroxyurea is permitted more than 24 hours before the first dose of study drug), radiotherapy, surgery, immunotherapy, targeted therapy, biological therapy or any investigational treatment.
7. Within 7 days before the first dose of study drug, received a strong and/or moderate CYP3A inducer and/or Inhibitor.
8. At the discretion of the investigator, gastrointestinal diseases that affect the absorption of Lisaftoclax (APG-2575).
9. Any other condition or circumstance, at the discretion of the investigator, that patients would be unsuitable for participation in the study.

Where this trial is running

Beijing, Beijing Municipality and 11 other locations

• Peking University People's Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Chongqing University Cancer Hospital — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guandong, China (Recruiting)
• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• Henan Tumor Hospital — Zhengzhou, Henan, China (Recruiting)
• Union Hospital medical college Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Zhongnan Hospital of Hunan university — Wuhan, Hubei, China (Recruiting)
• Xiangya Hospital Central South University — Changsha, Hunan, China (Recruiting)
• The First affiliated hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• Shanghai The Sixth People' s Hospital — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)
• the First Affiliated Hospital, College of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jie Jin, M.D. — the First Affiliated Hospital, College of Medicine
• Study coordinator: Jie Jin, M.D.

Conditions Relapsed/Refractory Acute Myeloid Leukaemia; Myeloid Malignancy; Acute Myeloid Leukaemia; Bcl-2 Inhibitor; Lisaftoclax