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

Recruiting now · Phase 1

Conditions studied: Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS)

In brief

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).

Key facts

Study ID

NCT04275518

Run by

Ascentage Pharma Group Inc.

People needed

102

Starts

2020-07-06

Expected to finish

2025-12-31

Last updated by the study team

2024-10-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Age >/= 18 years.
• Adequate organ function
• Subject must have a projected life expectancy of at least 12 weeks.
• ECOG performance status of 0-1.
• 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.
• Subject has a white blood cell count< 50 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.

You may not qualify if…

• Subject has acute promyelocytic leukemia.
• 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)
• 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.
• Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
• Participants who have received allogeneic HSCT, or autologous HSCT within 12 months.
• Patients with active, uncontrolled CNS leukemia will not be eligible.
• Any prior systemic MDM2-p53 inhibitor treatment
• Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
• 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.

Where it is running

• Shanghai Jiao Tong University school of medicine Ruijing Hospital — Shanghai, Shanghai Municipality, China (enrolling)
• Shanghai Sixth people's Hospital — Shanghai, Shanghai Municipality, China (enrolling)
• Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (enrolling)
• Henan Provincial Oncology Hospital — Zhengzhou, Henan, China (enrolling)
• Union Hospital medical college Huazhong University of Science and Technology — Wuhan, Hubei, China (enrolling)
• Zhongnan Hospital of Wuhan University — Wuhan, Hubei, China (enrolling)
• Xiangya Hospital Central South University — Changsha, Hunan, China (enrolling)
• Guangzhou panyu central hospital — Guangzhou, Guangdong, China (enrolling)
• The First affiliated hospital of Soochow University — Suzhou, Jiangsu, China (enrolling)
• Nanfang Hospital of Southern Medical University — Guangzhou, Guangdong, China (enrolling)
• First Hospital of Jilin University — Changchun, Jilin, China (enrolling)
• The First Affilated Hospital of Ganzhou Medical University — Suzhou, Jiangsu, China
• The First Hospital of Peking University — Beijing, Beijing Municipality, China
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China

Full record on ClinicalTrials.gov

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