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

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04501120
• Other study ID #: APG2575AC101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 28, 2020
• Est. completion date: August 2025

Study information

• Verified date: May 2024
• Source: Ascentage Pharma Group Inc.
• Contact: Jie Jin, M.D.
• Phone: +86 571-87236896
• Email: jiej0503[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myeloid Malignancy
• Neoplasms
• Relapsed/Refractory Acute Myeloid Leukaemia

Intervention

Drug:
• APG-2575
APG-2575 orally once daily, every 28 days as a cycle.
• Reduced-dose HHT
1mg IV QD on Days 1-14 (28-day cycle).
• standard-dose HHT
2mg/m^2 IV QD on Days 1-7 (28-day cycle).
• Azacitidine
75 mg/m^2 SC or Iv gtt QD on Days 1- 7 (28-day cycle).
• APG-2575
APG-2575 orally once daily for 14 days, every 28 days as a cycle.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Ascentage Pharma Group Inc.	Suzhou Yasheng Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

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.