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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
682
Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.
1mg IV QD on Days 1-14 (28-day cycle).
2mg/m\^2 IV QD on Days 1-7 (28-day cycle).
Peking University People's Hospital
Beijing, Beijing Municipality, China
RECRUITINGChongqing University Cancer Hospital
Chongqing, Chongqing Municipality, China
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.
Time frame: 28 days
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)
MTD/RP2D will be determined based on DLTs observed during cycle one.
Time frame: 28 days
Maximum plasma concentration (Cmax)
Cmax of Lisaftoclax (APG-2575) will be assessed in the patients in single agent or combo study.
Time frame: 28 days
Area under the plasma concentration versus time curve (AUC)
AUC of Lisaftoclax (APG-2575) will be assessed in the patients in single agent or combo study.
Time frame: 28 days
Objective Response Rate (ORR)
ORR is defined by CR+ CRi + PR(according to IWG AML(2003)).Response will be evaluated on cycle 1 and every even cycles till completing 6 cycles treatment or end of treatment.
Time frame: Up to 6 cycles (each cycle is 28 days).
progression free survival (PFS)
From date of treatment start until the date of progression or the date of death due to any cause.
Time frame: Up to 2 years.
duration of response (DOR)
From date of response until the date of progression.
Time frame: Up to 2 years.
overall survival (OS)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).
Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.
orally, with meals, QOD, every 28 days as a cycle.
Sun Yat-sen University Cancer Center
Guangzhou, Guandong, China
RECRUITINGGuangdong Provincial People's Hospital
Guangzhou, Guangdong, China
RECRUITINGHenan Tumor Hospital
Zhengzhou, Henan, China
RECRUITINGUnion Hospital medical college Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGZhongnan Hospital of Hunan university
Wuhan, Hubei, China
RECRUITINGXiangya Hospital Central South University
Changsha, Hunan, China
RECRUITINGThe First affiliated hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGShanghai The Sixth People' s Hospital
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITING...and 2 more locations
From date of treatment start until the date of death due to any cause.
Time frame: Up to 2 years.