A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.

NCT ID: NCT04275518

Last Updated: 2024-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-06

Study Completion Date

2025-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Acute myeloid leukemia is a malignant disorder characterized by the rapid, uncontrolled proliferation of malignant clonal hematopoietic stem cells that accumulate as immature, undifferentiated cells (blasts) in the bone marrow and circulation.

APG-115 is a potent and orally active small-molecule MDM2 inhibitor, it binds to MDM2 protein and shows potent cell growth inhibitory activity in vitro with low nanomolar potencies in a subset of human cancer cell lines. APG-115 has demonstrated its strong antitumor activities with either daily or less frequent dosing-schedules in the acute leukemia xenograft models.

This is a phase 1b, open-label, three-stages study that will initially evaluate the safety and PK/PD profile of APG-115 as a single agent, followed by a combination of APG-115 + azacytidine or cytarabine in R/R AML or MDS subjects.

Patients will continue treatment for maximally 6 cycles or until progression of disease or unacceptable toxicity is observed or administrative discontinuation whichever occurs first. Patients who continue to be benefit after 6 cycles' treatment will receive additional cycles of treatment until progression of disease, unacceptable toxicity is observed or administrative discontinuation. (As long as it is proven safe).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Stage 1: This will be a 3+3 dose escalation to determine the DLTs and MTD/RP2D of APG-115 given according to the different dose levels once daily from Days 1 to 7 every 28 days.

Stage 2: After stage 1 of APG-115 single agent dose escalation first cycle is completed, stage 2 can be initiated with the combination regimen. This will be a 3+3 dose escalation to determine the MTD/RP2D and DLTs of APG-115 + AZA(arm A)/Cytarabine (arm B)combination.

Stage 3: dose expansion of the combination regimes.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Myeloid Leukemia (AML) Myelodysplastic Syndromes (MDS)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

APG-115/APG-115+Cytarabine in Relapse/Refractory AML

Group Type EXPERIMENTAL

APG-115

Intervention Type DRUG

APG-115 orally once daily from Days 1 to 7 every 28 days.

Cytarabine

Intervention Type DRUG

1g/m\^2 IV QD on Days 3-7 (28-day cycle)

APG-115/APG-115+Aza in relapsed/progressed high risk MDS

Group Type EXPERIMENTAL

APG-115

Intervention Type DRUG

APG-115 orally once daily from Days 1 to 7 every 28 days.

Azacitidine

Intervention Type DRUG

75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

APG-115

APG-115 orally once daily from Days 1 to 7 every 28 days.

Intervention Type DRUG

Azacitidine

75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle)

Intervention Type DRUG

Cytarabine

1g/m\^2 IV QD on Days 3-7 (28-day cycle)

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia by WHO classification or relapsed/progressed high/very high risk MDS (score≥4.5) according to IPSS-R risk stratification
2. Age \>/= 18 years.
3. Adequate organ function
4. Subject must have a projected life expectancy of at least 12 weeks.
5. ECOG performance status of 0-1.
6. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
7. Subject has a white blood cell count\< 50 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.

Exclusion Criteria

1. Subject has acute promyelocytic leukemia.
2. Patients must not have had leukemia biotherapy 4 weeks prior to starting investigational drug, or less than 5 half-lives small molecular targeted drug therapy, or 28 days any anti-cancer therapy (whichever is longer)
3. Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
5. Participants who have received allogeneic HSCT, or autologous HSCT within 12 months.
6. Patients with active, uncontrolled CNS leukemia will not be eligible.
7. Any prior systemic MDM2-p53 inhibitor treatment
8. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
9. Subject has a history of other malignancies within 2 years prior to study entry, with the exception of:

* Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
* Previous malignancy confined and surgically resected (or treated with other modalities) with curative intention: requires discussion with sponsor.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Suzhou Yasheng Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Ascentage Pharma Group Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jianxiang Wang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Blood Diseases Hospital Chinese Academy of Medical Sciences

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The First Hospital of Peking University

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

Guangzhou panyu central hospital

Guangzhou, Guangdong, China

Site Status RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Henan Provincial Oncology Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Union Hospital medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, China

Site Status RECRUITING

The First Affilated Hospital of Ganzhou Medical University

Suzhou, Jiangsu, China

Site Status NOT_YET_RECRUITING

The First affiliated hospital of Soochow University

Suzhou, Jiangsu, China

Site Status RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status NOT_YET_RECRUITING

First Hospital of Jilin University

Changchun, Jilin, China

Site Status RECRUITING

Shanghai Jiao Tong University school of medicine Ruijing Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanghai Sixth people's Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Junyuan Qi, M.D.

Role: CONTACT

+86-18622662361

Bo Jiang, M.D.

Role: CONTACT

+86-22-23909067

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Qian Jiang, Ph.D

Role: primary

Shuqin Cheng, Master

Role: primary

Hui Yang Professor

Role: backup

Yu Zhang, Master

Role: primary

Chongyuan Xu Professor

Role: backup

86-020-62786845

Xudong Wei, M.D.

Role: primary

Qiubo Li, Doctor

Role: primary

Fuling Zhou, M.D.

Role: primary

Jianying Huang Director

Role: backup

Qun He, Master

Role: primary

Qun Qin, M.D.

Role: backup

Liping Liu, Ph.D.

Role: primary

Xiaowen Tang, Doctor

Role: primary

Fei Li, Ph.D.

Role: primary

Sujun Gao, M.D.

Role: primary

Junmin Li Professor

Role: primary

Chunkang Chang Professor

Role: primary

Jianxiang Wang, MD

Role: primary

+86 22-23909120

Junyuan Qi, MD

Role: backup

+86 18622662361

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

APG115AC101

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.