Study of Lisaftoclax (APG-2575) Single Agent and Combination With Therapy in Patients Relapsed/Refractory AML
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
1 other identifier
interventional
682
1 country
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2020
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 3, 2020
CompletedFirst Posted
Study publicly available on registry
August 6, 2020
CompletedStudy Start
First participant enrolled
September 28, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2029
April 29, 2026
April 1, 2026
7.9 years
August 3, 2020
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Dose Limiting Toxicities (DLT)
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during cycle one.
28 days
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)
MTD/RP2D will be determined based on DLTs observed during cycle one.
28 days
Secondary Outcomes (6)
Maximum plasma concentration (Cmax)
28 days
Area under the plasma concentration versus time curve (AUC)
28 days
Objective Response Rate (ORR)
Up to 6 cycles (each cycle is 28 days).
progression free survival (PFS)
Up to 2 years.
duration of response (DOR)
Up to 2 years.
- +1 more secondary outcomes
Study Arms (8)
Lisaftoclax (APG-2575) single agent
EXPERIMENTALLisaftoclax (APG-2575) orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg, to determine the MTD/RP2D.
Lisaftoclax (APG-2575)+reduced-dose HHT
EXPERIMENTALLisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with reduced-dose HHT in R/R AML, MPAL, BPDCN, CMML.
Lisaftoclax (APG-2575)+ standard-dose HHT
EXPERIMENTALLisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with standard-dose HHT in R/R AML, MPAL, BPDCN, CMML.
Lisaftoclax (APG-2575)+ AZA
EXPERIMENTALLisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in R/R AML, MPAL, BPDCN, CMML.
Lisaftoclax (APG-2575)+ AZA(HR-MDS.)
EXPERIMENTALLisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in HR-MDS.
Lisaftoclax (APG-2575)+ AZA(Naïve AML.)
EXPERIMENTALLisaftoclax (APG-2575) MTD/RP2D-1 and MTD/RP2D combines with AZA in treatment naïve AML.
Lisaftoclax (APG-2575)+AZA+Olverembatinib
EXPERIMENTALLisaftoclax (APG-2575) combines with AZA and Olverembatinib in R/R AML.
Lisaftoclax (APG-2575)+HHT+Olverembatinib
EXPERIMENTALLisaftoclax (APG-2575) combines with HHT and Olverembatinib in R/R AML.
Interventions
2mg/m\^2 IV QD on Days 1-7 (28-day cycle).
75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).
Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.
orally, with meals, QOD, every 28 days as a cycle.
Eligibility Criteria
You may qualify if:
- 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.
- 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).
- Subjects can accept oral administration of Lisaftoclax (APG-2575).
- Life expectancy ≥ 3 months.
- Adequate renal and liver function.
- 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.
- 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).
- Willingness and ability to comply with study procedures and follow-up examination.
You may not qualify if:
- Patients diagnosed with acute promyelocytic leukemia or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML patients.
- 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).
- Known leukemia infiltration of the central nervous system.
- Symptomatic active fungal, bacterial and/or viral infections.
- Prior history of allogeneic hematopoietic stem cell transplantation or adoptive cell immunotherapy, autologous hematopoietic stem cell transplantation within 12 months.
- 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.
- Within 7 days before the first dose of study drug, received a strong and/or moderate CYP3A inducer and/or Inhibitor.
- At the discretion of the investigator, gastrointestinal diseases that affect the absorption of Lisaftoclax (APG-2575).
- Any other condition or circumstance, at the discretion of the investigator, that patients would be unsuitable for participation in the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Peking University People's Hospital
Beijing, Beijing Municipality, 100044, China
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, China
Sun Yat-sen University Cancer Center
Guangzhou, Guandong, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510080, China
Henan Tumor Hospital
Zhengzhou, Henan, China
Union Hospital medical college Huazhong University of Science and Technology
Wuhan, Hubei, 430022, China
Zhongnan Hospital of Hunan university
Wuhan, Hubei, 430071, China
Xiangya Hospital Central South University
Changsha, Hunan, China
The First affiliated hospital of Soochow University
Suzhou, Jiangsu, China
Shanghai The Sixth People' s Hospital
Shanghai, Shanghai Municipality, China
West China Hospital of Sichuan University
Chengdu, Sichuan, 610044, China
the First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Yifan Zhai, M.D., Ph.D.
Suzhou Yasheng Pharmaceutical Co., Ltd.
- PRINCIPAL INVESTIGATOR
Jie Jin, M.D.
the First Affiliated Hospital, College of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 3, 2020
First Posted
August 6, 2020
Study Start
September 28, 2020
Primary Completion (Estimated)
September 1, 2028
Study Completion (Estimated)
September 1, 2029
Last Updated
April 29, 2026
Record last verified: 2026-04