Overview

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.

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.