Clinical trial NCT04501120: Study of APG2575 Single Agent and Combination With Therapy in Patients Relapsed/Refractory AML
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Acute Myeloid Leukaemia
Myeloid Malignancy
Keywords: APG-2575
Acute Myeloid Leukaemia (AML)
Bcl-2 Inhibitor
Myeloid Malignancy
Lead sponsor: Ascentage Pharma Group Inc.
Sponsor class: INDUSTRY
Collaborators: name: Suzhou Yasheng Pharmaceutical Co., Ltd.
First posted: 2020-08-06
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This is an open-label, multi-center Phase Ib study of safety, PK of 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 APG-2575 single agent dose-escalation study. The second stage is the APG-2575 combined with HHT/AZA dose-escalation study. The third stage is the MTD/RP2D expansion cohort study of the combination regimen.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)
timeFrame: 28 days
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 days
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 28 days
measure: Objective Response Rate (ORR)
timeFrame: Up to 6 cycles (each cycle is 28 days).
measure: progression free survival (PFS)
timeFrame: Up to 2 years.
measure: duration of response (DOR)
timeFrame: Up to 2 years.
measure: overall survival (OS)
timeFrame: Up to 2 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guandong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital medical college Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Hunan university
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Suzhou
country: China
facility: The First affiliated hospital of Soochow University
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai The Sixth People' s Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: the First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Suzhou Yasheng Pharmaceutical Co., Ltd.
name: Yifan Zhai, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: the First Affiliated Hospital, College of Medicine
name: Jie Jin, M.D.
role: PRINCIPAL_INVESTIGATOR
References: