Lisaftoclax (APG-2575): Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.
Reduced-dose HHT: 1mg IV QD on Days 1-14 (28-day cycle).
standard-dose HHT: 2mg/m\^2 IV QD on Days 1-7 (28-day cycle).
Azacitidine: 75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).
Lisaftoclax (APG-2575): Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.
olverembatinib: orally, with meals, QOD, every 28 days as a cycle.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Dose Limiting Toxicities (DLT) — 28 days 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.
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D) — 28 days MTD/RP2D will be determined based on DLTs observed during cycle one.
Trial sites (12)
Facility
City
Region
Status
Peking University People's Hospital
Beijing
Beijing Municipality
Recruiting
Chongqing University Cancer Hospital
Chongqing
Chongqing Municipality
Not Yet Recruiting
Sun Yat-sen University Cancer Center
Guangzhou
Guandong
Recruiting
Guangdong Provincial People's Hospital
Guangzhou
Guangdong
Recruiting
Henan Tumor Hospital
Zhengzhou
Henan
Recruiting
Union Hospital medical college Huazhong University of Science and Technology
Wuhan
Hubei
Recruiting
Zhongnan Hospital of Hunan university
Wuhan
Hubei
Recruiting
Xiangya Hospital Central South University
Changsha
Hunan
Recruiting
The First affiliated hospital of Soochow University
Suzhou
Jiangsu
Recruiting
Shanghai The Sixth People' s Hospital
Shanghai
Shanghai Municipality
Not Yet Recruiting
West China Hospital of Sichuan University
Chengdu
Sichuan
Recruiting
the First Affiliated Hospital, College of Medicine, Zhejiang University
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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