RecruitingPhase 1Phase 2NCT04501120

Study of Lisaftoclax (APG-2575) Single Agent and Combination With Therapy in Patients Relapsed/Refractory AML

A Phase Ib Study of the Safety, Pharmacokinetic of Lisaftoclax (APG-2575) Single Agent and in Combination With Homoharringtonine or Azacitidine in Patients With Relapsed/Refractory AML


Sponsor

Ascentage Pharma Group Inc.

Enrollment

458 participants

Start Date

Sep 28, 2020

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria8

  • 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.
  • 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).
  • Subjects can accept oral administration of Lisaftoclax (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 Criteria9

  • Patients diagnosed with acute promyelocytic leukemia or t(9;22)(q34.1;q11.2); BCR-ABL1 positive AML patients.
  • 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.
  • Prior history of allogeneic hematopoietic stem cell transplantation or adoptive cell immunotherapy, autologous hematopoietic stem cell transplantation within 12 months.
  • 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.
  • Within 7 days before the first dose of study drug, received a strong and/or moderate CYP3A inducer and/or Inhibitor.
  • At the discretion of the investigator, gastrointestinal diseases that affect the absorption of Lisaftoclax (APG-2575).
  • Any other condition or circumstance, at the discretion of the investigator, that patients would be unsuitable for participation in the study.

Interventions

DRUGLisaftoclax (APG-2575)

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).

DRUGLisaftoclax (APG-2575)

Lisaftoclax (APG-2575) orally once daily for 14 days, every 28 days as a cycle.

DRUGolverembatinib

orally, with meals, QOD, every 28 days as a cycle.


Locations(12)

Peking University People's Hospital

Beijing, Beijing Municipality, China

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Sun Yat-sen University Cancer Center

Guangzhou, Guandong, China

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Henan Tumor Hospital

Zhengzhou, Henan, China

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

Zhongnan Hospital of Hunan university

Wuhan, Hubei, China

Xiangya Hospital Central South University

Changsha, Hunan, China

The First affiliated hospital of Soochow University

Suzhou, Jiangsu, China

Shanghai The Sixth People' s Hospital

Shanghai, Shanghai Municipality, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

the First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

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NCT04501120


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