Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory AML
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
  • Phase

    Phase 1/Phase 2
  • Study Type

  • Status

  • Study Participants

The purpose of this study is to assess the safety, pharmacokinetic of 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 APG-2575 as a 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 APG-2575 single agent escalation study. The second stage is the APG-2575 combined with HHT/AZA escalation study. The third stage is the MTD/RP2D expansion cohort study of the combination regimen.
Study Started
Sep 28
Primary Completion
Aug 31
Study Completion
Aug 31
Last Update
Jan 12

Drug APG-2575

APG-2575 orally once daily, every 28 days as a cycle.

Drug reduced-dose HHT

1mg IV QD on Days 1-14 (28-day cycle).

Drug standard-dose HHT

2mg/m^2 IV QD on Days 1-7 (28-day cycle).

Drug Azacitidine

75 mg/m^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).

APG2575 single agent Experimental

APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg, to determine the MTD/RP2D.

APG2575+ reduced-dose HHT Experimental

APG-2575 MTD/RP2D-1 and MTD/RP2D combines with reduced-dose HHT.

APG2575+ standard-dose HHT Experimental

APG-2575 MTD/RP2D-1 and MTD/RP2D combines with standard-dose HHT.

APG2575+ AZA Experimental

APG-2575 MTD/RP2D-1 and MTD/RP2D combines with AZA.


Inclusion Criteria:

Subjects who meet each of the following inclusion criteria are eligible to participate in this study:

Age ≥18 years old.
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) and Blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2.
Subjects can accept oral administration of APG-2575.
Life expectancy ≥ 3 months.
Adequate renal and liver function.
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.
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).
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:

Patients diagnosed as acute promyelocytic leukemia (FAB classification AML-M3 or WHO diagnosis classification APL with PML-RARα) or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML patients.
White blood cell (WBC) ≥100×109/L when screening.
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).
Known leukemia infiltration of the central nervous system.
Symptomatic active fungal, bacterial and/or viral infections, including but not limited to active human immunodeficiency virus (HIV), viral hepatitis B or C (type B or C).
Prior history of allogeneic hematopoietic stem cell transplantation or adoptive cell immunotherapy or autologous hematopoietic stem cell transplantation within 12 months.
Requirement of therapeutic doses of anticoagulants and antiplatelet drugs, but allow the use of low doses of anticoagulants to maintain the opening of the central venous catheter.
Within 14 days before the first dose of study drug, received chemotherapy (hydroxyurea is permitted more than 48 hours before the first dose of study drug), radiotherapy, surgery, immunotherapy, hormone therapy, targeted therapy, biological therapy or Chinese herbal therapy or any investigational treatment.
Within 7 days before the first dose of study drug, received a strong and/or moderate CYP3A inducer and/or Inhibitor.
Within 7 days before the first dose of study drug, received hematopoietic cytokines (granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or erythropoietin) .
Failure to recover adequately, at the discretion of the investigator, from prior surgical procedures, including patients who have had major surgery within 28 days before the first dose of study drug, and patients who have had minor surgery (excluding pathological biopsy) within 14 days before the beginning of study.
At the discretion of the investigator, gastrointestinal diseases that affect the absorption of APG-2575.
Unstable angina, myocardial infarction, coronary artery reconstruction, or severe gastrointestinal bleeding occurred during the 180 days before the start of study.
Uncontrolled complications include but not limited to: uncontrollable severe infections, symptomatic congestive heart failure, unstable angina, arrhythmia, or mental illness/social environment that may affect compliance.
The last treatment before signing the informed consent was a Bcl-2 inhibitor (subjects who had been treated with a Bcl-2 inhibitor but had not developed drug resistance could be enrolled in this study).
Any other condition or circumstance, at the discretion of the investigator, that patients would be unsuitable for participation in the study.
No Results Posted