Acute Myeloid Leukemia (AML)Phase 1NCT04275518
A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.
A Phase 1 study testing APG-115, Azacitidine and Cytarabine in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS), run by Ascentage Pharma Group Inc. at 14 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS)
- What is being tested?
- APG-115, Azacitidine and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 14 sitesChina
- Study dates
- 6 Jul 2020to 31 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
China14 sites, 14 recruiting
- Not yet recruiting
The First Hospital of Peking University
Beijing, Beijing Municipality, 100034
Qian Jiang, Ph.D
Qian Jiang, Ph.D
- Recruiting
First Hospital of Jilin University
Changchun, Jilin
Sujun Gao, M.D.
- Recruiting
Xiangya Hospital Central South University
Changsha, Hunan
Qun He, Master
Qun Qin, M.D.
- Recruiting
Guangzhou panyu central hospital
Guangzhou, Guangdong
Shuqin Cheng, Master
Hui Yang Professor
- Recruiting
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong
Yu Zhang, Master
Chongyuan Xu Professor, 86-020-62786845, nfyygcp@126.com
- Not yet recruiting
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Fei Li, Ph.D.
Fei Li, Ph.D.
- Recruiting
Shanghai Jiao Tong University school of medicine Ruijing Hospital
Shanghai, Shanghai Municipality
Junmin Li Professor
- Recruiting
Shanghai Sixth people's Hospital
Shanghai, Shanghai Municipality
Chunkang Chang Professor
- Not yet recruiting
The First Affilated Hospital of Ganzhou Medical University
Suzhou, Jiangsu, 215636
Liping Liu, Ph.D.
Liping Liu, Ph.D.
- Recruiting
The First affiliated hospital of Soochow University
Suzhou, Jiangsu
Xiaowen Tang, Doctor
- Recruiting
Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
Jianxiang Wang, MD, +86 22-23909120, wangjx@ihcams.ac.cn
Junyuan Qi, MD, +86 18622662361, qi_jy@yahoo.com
- Recruiting
Union Hospital medical college Huazhong University of Science and Technology
Wuhan, Hubei
Qiubo Li, Doctor
- Recruiting
Zhongnan Hospital of Wuhan University
Wuhan, Hubei
Fuling Zhou, M.D.
Jianying Huang Director
- Recruiting
Henan Provincial Oncology Hospital
Zhengzhou, Henan
Xudong Wei, M.D.
About this study
Official title: 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
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.
Read more
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).
Read the detailed description
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.
- Being tested
- APG-115, Azacitidine, Cytarabine
- Keywords
- APG-115, AML, MDS
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-115Drug
APG-115 orally once daily from Days 1 to 7 every 28 days.
AzacitidineDrug
75 mg/m^2 SC QD on Days 1- 7 (28-day cycle)
CytarabineDrug
1g/m^2 IV QD on Days 3-7 (28-day cycle)
| Study group | Role | What they receive |
|---|---|---|
| APG-115/APG-115+Cytarabine in Relapse/Refractory AML | Experimental | Not described Receives: Drug: APG-115; Drug: Cytarabine |
| APG-115/APG-115+Aza in relapsed/progressed high risk MDS | Experimental | Not described Receives: Drug: APG-115; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From day 1 to the end of cycle 1 (each cycle is 28 days).
Secondary outcomes (2)
Overall Response Rate (ORR)
ORR is defined by CR + CRi+ PR (according to IWG AML（2003）and IWG MDS（2006）criteria)
Measured: 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)
From date of treatment start until the date of death due to any cause or date of termination of the study, whichever came first. Termination of the Study: The last subject has completed at least 6 cycle's treatment or the subject discontinues treatment for any reason.
Measured: Measured up to 6 months after the last subject has received treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2020
- Study start6 Jul 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Suzhou Yasheng Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Jianxiang Wang, M.D., Principal investigator, Blood Diseases Hospital Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04275518
- Sponsor's protocol ID
- APG115AC101
- Status last verified
- Oct 2024
- First submitted
- 5 Feb 2020
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04275518
- Acronym / sponsor ID
- APG115AC101
- Keywords
- APG-115, AML, MDS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Collaborators
- Suzhou Yasheng Pharmaceutical Co., Ltd.
- Study start
- 6 Jul 2020 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 19 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APG-115/APG-115+Cytarabine in Relapse/Refractory AML | Experimental | Drug: APG-115, Drug: Cytarabine |
| APG-115/APG-115+Aza in relapsed/progressed high risk MDS | Experimental | Drug: APG-115, Drug: Azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APG-115APG-115 orally once daily from Days 1 to 7 every 28 days. | Drug | APG-115/APG-115+Aza in relapsed/progressed high risk MDS, APG-115/APG-115+Cytarabine in Relapse/Refractory AML |
| Azacitidine75 mg/m^2 SC QD on Days 1- 7 (28-day cycle) | Drug | APG-115/APG-115+Aza in relapsed/progressed high risk MDS |
| Cytarabine1g/m^2 IV QD on Days 3-7 (28-day cycle) | Drug | APG-115/APG-115+Cytarabine in Relapse/Refractory AML |
Primary outcome
Dose Limiting Toxicities (DLT)
Time frame: From day 1 to the end of cycle 1 (each cycle is 28 days).
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.
2 secondary outcomes
Overall Response Rate (ORR)
Time frame: 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)
Time frame: Measured up to 6 months after the last subject has received treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jianxiang Wang, M.D. principal investigator
Blood Diseases Hospital Chinese Academy of Medical Sciences
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APG-115, Azacitidine and Cytarabine in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS), run by Ascentage Pharma Group Inc. at 14 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Junyuan Qi, M.D. (+86-18622662361, qi_jy@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicities (DLT) (time frame: From day 1 to the end of cycle 1 (each cycle is 28 days).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.