Myeloid Malignancy Clinical Trial
Official title:
A Phase Ib Study of the Safety, Pharmacokinetic of APG-2575 Single Agent and in Combination With Homoharringtonine or Azacitidine in Patients With Relapsed/Refractory AML
The purpose of this study is to assess the safety, pharmacokinetic profile of APG-2575 single agent and in combination with HHT/AZA in patients with relapsed/refractory AML and related myeloid malignancies.
Status | Recruiting |
Enrollment | 284 |
Est. completion date | August 2025 |
Est. primary completion date | August 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 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 APG-2575. 9. Any other condition or circumstance, at the discretion of the investigator, that patients would be unsuitable for participation in the study. |
Country | Name | City | State |
---|---|---|---|
China | Peking University People's Hospital | Beijing | Beijing |
China | Xiangya Hospital Central South University | Changsha | Hunan |
China | West China Hospital of Sichuan University | Chengdu | Sichuan |
China | Chongqing University Cancer Hospital | Chongqing | Chongqing |
China | Guangdong Provincial People's Hospital | Guangzhou | Guangdong |
China | Sun Yat-sen University Cancer Center | Guangzhou | Guandong |
China | the First Affiliated Hospital, College of Medicine, Zhejiang University | Hangzhou | Zhejiang |
China | Shanghai The Sixth People' s Hospital | Shanghai | Shanghai |
China | The First affiliated hospital of Soochow University | Suzhou | Jiangsu |
China | Union Hospital medical college Huazhong University of Science and Technology | Wuhan | Hubei |
China | Zhongnan Hospital of Hunan university | Wuhan | Hubei |
China | Henan Tumor Hospital | Zhengzhou | Henan |
Lead Sponsor | Collaborator |
---|---|
Ascentage Pharma Group Inc. | Suzhou Yasheng Pharmaceutical Co., Ltd. |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D) | MTD/RP2D will be determined based on DLTs observed during cycle one. | 28 days | |
Secondary | Maximum plasma concentration (Cmax) | Cmax of APG-2575 will be assessed in the patients in single agent or combo study. | 28 days | |
Secondary | Area under the plasma concentration versus time curve (AUC) | AUC of APG-2575 will be assessed in the patients in single agent or combo study. | 28 days | |
Secondary | 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. | Up to 6 cycles (each cycle is 28 days). | |
Secondary | progression free survival (PFS) | From date of treatment start until the date of progression or the date of death due to any cause. | Up to 2 years. | |
Secondary | duration of response (DOR) | From date of response until the date of progression. | Up to 2 years. | |
Secondary | overall survival (OS) | From date of treatment start until the date of death due to any cause. | Up to 2 years. |
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