Relapsed/Refractory Acute Myeloid Leukaemia, Myeloid Malignancy
Conditions
Keywords
Acute Myeloid Leukaemia (AML), Bcl-2 Inhibitor, Myeloid Malignancy, Lisaftoclax (APG-2575)
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.
Detailed description
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.
Interventions
Lisaftoclax (APG-2575) orally once daily, every 28 days as a cycle.
DRUGReduced-dose HHT
1mg IV QD on Days 1-14 (28-day cycle).
DRUGstandard-dose HHT
2mg/m\^2 IV QD on Days 1-7 (28-day cycle).
DRUGAzacitidine
75 mg/m\^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).
DRUGolverembatinib
orally, with meals, QOD, every 28 days as a cycle.
Sponsors
Suzhou Yasheng Pharmaceutical Co., Ltd.
Ascentage Pharma Group Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 6 cycles (each cycle is 28 days). | 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. |
| progression free survival (PFS) | Up to 2 years. | From date of treatment start until the date of progression or the date of death due to any cause. |
| Maximum plasma concentration (Cmax) | 28 days | Cmax of Lisaftoclax (APG-2575) will be assessed in the patients in single agent or combo study. |
| overall survival (OS) | Up to 2 years. | From date of treatment start until the date of death due to any cause. |
| duration of response (DOR) | Up to 2 years. | From date of response until the date of progression. |
| Area under the plasma concentration versus time curve (AUC) | 28 days | AUC of Lisaftoclax (APG-2575) will be assessed in the patients in single agent or combo study. |
Countries
China
Contacts
Primary ContactJie Jin, M.D.
Outcome results
None listed