A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.
A Phase Ib Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of APG-115 as a Single Agent or in Combination With Azacitidine or Cytarabine in Patients With Relapse/Refractory AML and Relapsed/Progressed High/Very High Risk MDS
1 other identifier
interventional
102
1 country
14
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2020
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 5, 2020
CompletedFirst Posted
Study publicly available on registry
February 19, 2020
CompletedStudy Start
First participant enrolled
July 6, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2025
CompletedOctober 15, 2024
October 1, 2024
5.5 years
February 5, 2020
October 10, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Dose Limiting Toxicities (DLT)
DLT will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, version 5) by organ system. DLT will be defined as clinically significant drug-related adverse events during the Cycle one.
From day 1 to the end of cycle 1 (each cycle is 28 days).
Secondary Outcomes (2)
Overall Response Rate (ORR)
Evaluated for response by the end of cycle 1 and cycle 2, and then 2 months thereafter till complete 6 cycles treatment or 1 month after last dose (each cycle is 28 days).
Overall survival (OS)
Measured up to 6 months after the last subject has received treatment.
Study Arms (2)
APG-115/APG-115+Cytarabine in Relapse/Refractory AML
EXPERIMENTALAPG-115/APG-115+Aza in relapsed/progressed high risk MDS
EXPERIMENTALInterventions
APG-115 orally once daily from Days 1 to 7 every 28 days.
75 mg/m\^2 SC QD on Days 1- 7 (28-day cycle)
1g/m\^2 IV QD on Days 3-7 (28-day cycle)
Eligibility Criteria
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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
The First Hospital of Peking University
Beijing, Beijing Municipality, 100034, China
Guangzhou panyu central hospital
Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Henan Provincial Oncology Hospital
Zhengzhou, Henan, China
Union Hospital medical college Huazhong University of Science and Technology
Wuhan, Hubei, China
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, China
Xiangya Hospital Central South University
Changsha, Hunan, China
The First Affilated Hospital of Ganzhou Medical University
Suzhou, Jiangsu, 215636, China
The First affiliated hospital of Soochow University
Suzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
First Hospital of Jilin University
Changchun, Jilin, China
Shanghai Jiao Tong University school of medicine Ruijing Hospital
Shanghai, Shanghai Municipality, China
Shanghai Sixth people's Hospital
Shanghai, Shanghai Municipality, China
Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jianxiang Wang, M.D.
Blood Diseases Hospital Chinese Academy of Medical Sciences
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2020
First Posted
February 19, 2020
Study Start
July 6, 2020
Primary Completion
December 31, 2025
Study Completion
December 31, 2025
Last Updated
October 15, 2024
Record last verified: 2024-10