Study of Lisaftoclax (APG-2575) Single Agent and Combination With Therapy in Patients Relapsed/Refractory AML

NCT ID: NCT04501120

Last Updated: 2025-09-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

458 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-28

Study Completion Date

2029-09-30

Brief Summary

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The purpose of this study is to assess the safety, pharmacokinetic profile of Lisaftoclax (APG-2575) single agent and in combination with HHT/AZA in patients with relapsed/refractory AML and related myeloid malignancies.

Detailed Description

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This is an open-label, multi-center Phase Ib study of safety, PK of Lisaftoclax (APG-2575) as single agent or in combination with HHT or AZA in relapsed/refractory AML and related myeloid malignancies patients.

This study consists of three stages: The first stage is the Lisaftoclax (APG-2575) single agent dose-escalation study. The second stage is the Lisaftoclax (APG-2575) combined with HHT/AZA dose-escalation study. The third stage is the MTD/RP2D expansion cohort study of the combination regimen.

Conditions

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Relapsed/Refractory Acute Myeloid Leukaemia Myeloid Malignancy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lisaftoclax (APG-2575) single agent

Lisaftoclax (APG-2575) orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg, to determine the MTD/RP2D.

Group Type EXPERIMENTAL

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

Lisaftoclax (APG-2575)+reduced-dose HHT

Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with reduced-dose HHT in R/R AML, MPAL, BPDCN, CMML.

Group Type EXPERIMENTAL

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

Reduced-dose HHT

Intervention Type DRUG

1mg IV QD on Days 1-14 (28-day cycle).

Lisaftoclax (APG-2575)+ standard-dose HHT

Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with standard-dose HHT in R/R AML, MPAL, BPDCN, CMML.

Group Type EXPERIMENTAL

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

standard-dose HHT

Intervention Type DRUG

2mg/m\^2 IV QD on Days 1-7 (28-day cycle).

Lisaftoclax (APG-2575)+ AZA

Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in R/R AML, MPAL, BPDCN, CMML.

Group Type EXPERIMENTAL

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

Azacitidine

Intervention Type DRUG

75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

Lisaftoclax (APG-2575)+ AZA(HR-MDS.)

Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in HR-MDS.

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.

Lisaftoclax (APG-2575)+ AZA(Naïve AML.)

Lisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in treatment naïve AML.

Group Type EXPERIMENTAL

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

Azacitidine

Intervention Type DRUG

75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

Lisaftoclax (APG-2575)+AZA+Olverembatinib

Lisaftoclax (APG-2575) combines with AZA and Olverembatinib in R/R AML.

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.

olverembatinib

Intervention Type DRUG

orally, with meals, QOD, every 28 days as a cycle.

Lisaftoclax (APG-2575)+HHT+Olverembatinib

Lisaftoclax (APG-2575) combines with HHT and Olverembatinib in R/R AML.

Group Type EXPERIMENTAL

standard-dose HHT

Intervention Type DRUG

2mg/m\^2 IV QD on Days 1-7 (28-day cycle).

Lisaftoclax (APG-2575)

Intervention Type DRUG

Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.

olverembatinib

Intervention Type DRUG

orally, with meals, QOD, every 28 days as a cycle.

Interventions

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Lisaftoclax (APG-2575)

Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.

Intervention Type DRUG

Reduced-dose HHT

1mg IV QD on Days 1-14 (28-day cycle).

Intervention Type DRUG

standard-dose HHT

2mg/m\^2 IV QD on Days 1-7 (28-day cycle).

Intervention Type DRUG

Azacitidine

75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

Intervention Type DRUG

Lisaftoclax (APG-2575)

Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.

Intervention Type DRUG

olverembatinib

orally, with meals, QOD, every 28 days as a cycle.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Suzhou Yasheng Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Ascentage Pharma Group Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yifan Zhai, M.D., Ph.D.

Role: STUDY_DIRECTOR

Suzhou Yasheng Pharmaceutical Co., Ltd.

Jie Jin, M.D.

Role: PRINCIPAL_INVESTIGATOR

the First Affiliated Hospital, College of Medicine

Locations

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Peking University People's Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status NOT_YET_RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guandong, China

Site Status RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Site Status RECRUITING

Henan Tumor Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Zhongnan Hospital of Hunan university

Wuhan, Hubei, China

Site Status RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, China

Site Status RECRUITING

The First affiliated hospital of Soochow University

Suzhou, Jiangsu, China

Site Status RECRUITING

Shanghai The Sixth People' s Hospital

Shanghai, Shanghai Municipality, China

Site Status NOT_YET_RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

the First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jie Jin, M.D.

Role: CONTACT

+86 571-87236896

Facility Contacts

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Qiang Jiang, Professor

Role: primary

Yi Gong, M.D.

Role: primary

Yang Liang, Professor

Role: primary

Jianyu Wong, M.D.

Role: primary

Xudong Wei, Professor

Role: primary

Qiubo Li, Professor

Role: primary

Fuling Zhou, Professor

Role: primary

Jianying Zhou, Professor

Role: backup

Yajing Xu, Master

Role: primary

Qun He, Master

Role: backup

Suning Chen, M.D.

Role: primary

Chunkang Chang, Professor

Role: primary

Xiao Shuai, M.D.

Role: primary

18980606797

Jie Jin, M.D.

Role: primary

+86 571-87236896

Other Identifiers

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APG2575AC101

Identifier Type: -

Identifier Source: org_study_id

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