AMLPhase 1/2NCT04358393
A Study of APG-115 Alone or Combined With Azacitidine in Patients With AML, CMML, or MDS
A Phase 1/2 study testing APG-115 and 5-azacitidine in people with AML and Acute Myeloid Leukemia, run by Ascentage Pharma Group Inc. at 8 sites in United States.
Trial summary
This is a two Part study in patients with relapsed/refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high risk myelodysplastic syndrome (MDS) that will initially evaluate the safety and tolerability of APG-115 as a single agent in Part 1, followed by a combination of APG-115 +… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia
- What is being tested?
- APG-115 and 5-azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 8 sitesUnited States
- Study dates
- 4 Dec 2020to 30 Dec 2025
- Phase
- Phase 1/2
- 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 AML, CMML, or high-risk MDS (overall revised international prognostic scoring system (IPSS-R) score > 3, including intermediate, high, or very high risk) by World Health Organization (WHO) classification for which no available standard therapies are indicated or anticipated to result in a durable response.
- Adequate organ function as defined below:
- Liver function (total bilirubin < or = 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) <3 x ULN
- Kidney function (defined as a calculated creatinine clearance ≥ 60 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula)
- Known cardiac ejection fraction of > or = 45% within the past 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
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- A negative serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or legally authorized representative is required prior to their enrollment on the protocol.
- Subject must have a projected life expectancy of at least 12 weeks.
- Subject has a white blood cell count < 25 × 10˄9/L. Note: Hydroxyurea is permitted to meet this criteria.
Who cannot join
- Pregnant women are excluded.
- 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.
- Have had leukemia therapy for 14 days prior to starting investigational drug. However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study.
- Have acute promyelocytic leukemia.
- Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
- Have received allogeneic hematopoietic stem cell transplant (HSCT) within 12 months prior to the first dose, or who have active/ongoing graft-versus host disease (GVHD), or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose), or received autologous hematopoietic stem cell transplantation within 6 months prior to the first dose.
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- Documented hypersensitivity to any of the components of the therapy program
- Active, uncontrolled central nervous system (CNS) leukemia will not be eligible.
- Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use at least 1 form of barrier birth control (such as condom) prior to study entry and for the duration of study participation.
- 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.
- 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
- Failure to have recovered (Grade > 1) from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)
- Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) ≥470 msec
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Catinna Mallett, catinna.mallett@usoncology.com
Jonathan Huntzinger, Jonathan.huntzinger@usoncology.com
- Recruiting
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Patricia Gibson, Patricia.Gibson@usoncology.com
Kathryn Wilson, Kathryn.Wilson@usoncology.com
- Recruiting
Duke University
Durham, North Carolina, 27710
Christine Daly, 919-660-2077, christine.daly@duke.edu
Harry Erba, MD, PhD
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Lilliana Payne, Lilliana.Payne@usoncology.com
Hunfa Asghar, Hunfa.Asghar@usoncology.com
- Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Kevin Minahan, 480-256-5463, Kevin.Minahan@bannerhealth.com
Matthew Ulrickson, MD
- Recruiting
MD Anderson
Houston, Texas, 77030
Tapan Kadia, MD, 713-563-3534, tkadia@mdanderson.org
Tapan Kadia, MD
- Recruiting
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Mary-Elizabeth Percival, MD
- Recruiting
Texas Oncology - Tyler
Tyler, Texas, 75702
Penny Watkins, Penny.Watkins@usoncology.com
Habte Yimer, MD
About this study
Official title: A Phase Ib/II Study of APG-115 Alone or in Combination With Azacitidine in Patients With Relapse/Refractory AML, CMML or MDS
This is a two Part study in patients with relapsed/refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high risk myelodysplastic syndrome (MDS) that will initially evaluate the safety and tolerability of APG-115 as a single agent in Part 1, followed by a combination of APG-115 + 5-azacitidine (5-AZA) in Part 2.
Read the detailed description
Part 1: Dose escalation of APG-115 will use standard 3+3 design. APG-115 is administered orally once daily (QD) on Day 1-5 every 28-day cycle. The starting target dose is 100 mg (dose level; DL1) and will be increased in subsequent cohorts to 150 mg (DL2), 200 mg (DL3), and 250 mg (DL4), accordingly.
Part 2: Dose escalation of APG-115 in combination with 5-AZA will use standard 3+3 design. 5-AZA is administered at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days.
- Conditions
- AML, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, CMML, Myelodysplastic Syndromes, High-risk Myelodysplastic Syndrome
- Being tested
- APG-115, 5-azacitidine
- Keywords
- TP53
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, 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 given once daily on day 1-5 of every 28 day cycle
5-azacitidineDrug
Also called Vidaza, Azadine
5-AZA is given at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days
| Study group | Role | What they receive |
|---|---|---|
| APG-115 monotherapy | Experimental | Monotherapy given in part 1 Receives: Drug: APG-115 |
| APG-115 + 5-azacitidine combination | Experimental | Combination therapy given in part 2 Receives: Drug: APG-115; Drug: 5-azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
Part I is to assess the safety and tolerability of APG-115 by assessing the dose-limiting toxicity (DLT) of APG-115. End points include: Incidence of DLTs during the first 3 weeks of treatment of each dose cohort; Severity and frequency of any adverse event(s) (AE) and serious adverse event(s) (SAE) based on NCI CTCAE 5.0
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start4 Dec 2020
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AMLStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yifan Zhai, MD, PhD, Study chair, Ascentage Pharma Group Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04358393
- Sponsor's protocol ID
- APG115AU101
- Status last verified
- Jan 2024
- First submitted
- 21 Apr 2020
- Last updated
- 1 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of APG-115 Alone or in Combination With Azacitidine in Patients With Relapse/Refractory AML, CMML or MDS
- ClinicalTrials.gov ID
- NCT04358393
- Acronym / sponsor ID
- APG115AU101
- Conditions
- AML, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, CMML, Myelodysplastic Syndromes, High-risk Myelodysplastic Syndrome
- Keywords
- TP53
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Dec 2020 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 24 Apr 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.
This is a two Part study in patients with relapsed/refractory acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), or high risk myelodysplastic syndrome (MDS) that will initially evaluate the safety and tolerability of APG-115 as a single agent in Part 1, followed by a combination of APG-115 + 5-azacitidine (5-AZA) in Part 2.
Detailed description
Part 1: Dose escalation of APG-115 will use standard 3+3 design. APG-115 is administered orally once daily (QD) on Day 1-5 every 28-day cycle. The starting target dose is 100 mg (dose level; DL1) and will be increased in subsequent cohorts to 150 mg (DL2), 200 mg (DL3), and 250 mg (DL4), accordingly.
Part 2: Dose escalation of APG-115 in combination with 5-AZA will use standard 3+3 design. 5-AZA is administered at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APG-115 monotherapy | Experimental | Drug: APG-115Monotherapy given in part 1 |
| APG-115 + 5-azacitidine combination | Experimental | Drug: APG-115, Drug: 5-azacitidineCombination therapy given in part 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with a diagnosis of histologically confirmed relapsed or refractory AML, CMML, or high-risk MDS (overall revised international prognostic scoring system (IPSS-R) score > 3, including intermediate, high, or very high risk) by World Health Organization (WHO) classification for which no available standard therapies are indicated or anticipated to result in a durable response.
- Adequate organ function as defined below:
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- A negative serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or legally authorized representative is required prior to their enrollment on the protocol.
Key exclusion criteria (17 listed)
- Pregnant women are excluded.
- 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.
- Have had leukemia therapy for 14 days prior to starting investigational drug. However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study.
- Have acute promyelocytic leukemia.
- Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection.
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 given once daily on day 1-5 of every 28 day cycle | Drug | APG-115 + 5-azacitidine combination, APG-115 monotherapy |
| 5-azacitidineAlso: Vidaza, Azadine5-AZA is given at 75 mg/m˄2/d subcutaneously daily on Day 1-7 every 28 days | Drug | APG-115 + 5-azacitidine combination |
Primary outcome
Maximum Tolerated Dose
Time frame: 28 days
Part I is to assess the safety and tolerability of APG-115 by assessing the dose-limiting toxicity (DLT) of APG-115. End points include: Incidence of DLTs during the first 3 weeks of treatment of each dose cohort; Severity and frequency of any adverse event(s) (AE) and serious adverse event(s) (SAE) based on NCI CTCAE 5.0
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Individual participant dataSharing planned: No
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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.
Yifan Zhai, MD, PhD study chair
Ascentage Pharma Group Inc.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APG-115 and 5-azacitidine in people with AML and Acute Myeloid Leukemia, run by Ascentage Pharma Group Inc. at 8 sites in United States.
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 10 inclusion and 17 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 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Angela Kaiser (301-509-0357, Angela.Kaiser@ascentage.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: 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 1 Feb 2024.