AML, AdultPhase 1/2NCT04964518
A Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML)
A Phase 1/2 study testing APG 2575 ramp up arm in people with AML, Adult, run by Ascentage Pharma Group Inc. at 9 sites in 2 countries.
Trial summary
This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy and PK of APG-2575 in combination with Azacitidine in the patients with AML/MPAL or MDS/CMML. The study consists of dose escalation (Part I) and dose expansion phase (Part II) Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- AML, Adult
- What is being tested?
- APG 2575 ramp up arm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 30 Jul 2021to 30 Oct 2024
- 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 to 99 years
- 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 (AML) or mixed phenotype acute leukemia (MPAL) or Chronic Myelomonocytic Leukemia (CMML) or relapsed/refractory Higher-Risk MDS by 2016 WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response.
- MPAL will include biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population.
- Relapsed/refractory MDS will be defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy with Overall Revised International Prognostic Scoring System (IPSS-R) score > 3 (intermediate, high or very high).
Who cannot join
- Pregnant women.
- 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 within 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 taken strong inhibitors or inducers of CYP3A4 within 7 days prior to the first dose of APG-2575.
- Have acute promyelocytic leukemia (French-American-British Class M3 AML or WHO classification APL with PML-RARA) or AML/MPAL with BCR-ABL1 positive.
Show all 20Show fewer
- Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection or active COVID-19. (Patients who have received COVID-19 vaccination will be considered as eligible for the study.)
- 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).
- Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 6 months of study treatment initiation.
- Documented hypersensitivity to any of the components of the therapy program.
- Active, uncontrolled CNS leukemia.
- 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.
- 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), except for alopecia.
- Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- 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.
- Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States5 sites, 5 recruiting
- Recruiting
Novant Health
Charlotte, North Carolina, 28413
Patricia Kropf, MD
- Recruiting
MDACC
Houston, Texas, 77030
Debra B Linderman, 713-614-2069, DLBull@mdanderson.org
Tapan Kadia, MD
- Recruiting
UCLA Medical cetner Division of Hematology
Los Angeles, California, 94101
Caspian Oliai, MD
- Recruiting
Swedish Medical Center
Seattle, Washington, 98104
Daniel Egan, MD
- Recruiting
Novant Health
Winston-Salem, North Carolina, 27103
Patricia Kropf, MD, 980-302-4560
James Dugan, MD
Australia4 sites, 4 recruiting
- Recruiting
Pindara Private Hospital
Benowa, Queensland, 4217
Hanlon Sia, MD
- Recruiting
Sunshine Coast University Hospital
Birtinya, Queensland, 4575
Joshua Richmond, MD
- Recruiting
The Northern Hospital
Epping, Victoria, 3076
Chong C Chua, MD
- Recruiting
Royal Perth Hospital
Perth, Western Aus, 6000
Michael Leahy, MD
About this study
Official title: A Phase Ib/II Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML), Mixed Phenotype Acute Leukemia (MPAL), Chronic Myelomonocytic Leukemia (CMML) and Higher-Risk Myelodysplastic Syndrome (MDS
This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy and PK of APG-2575 in combination with Azacitidine in the patients with AML/MPAL or MDS/CMML. The study consists of dose escalation (Part I) and dose expansion phase (Part II)
Read the detailed description
The patients with histologically confirmed relapsed or refractory (R/R) AML/MPAL/CMML or relapsed/refractory Higher-Risk MDS by WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response will be enrolled.
This will be a 3+3 dose escalation to determine the DLTs and MTD/RP2D of APG-2575 (see dose escalation table) given in combination with Azacitidine
- Conditions
- AML, Adult
- Being tested
- APG 2575 ramp up arm
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG 2575 ramp up armDrug
Also called APG2575
APG2575 ramp up + Azacitidine
| Study group | Role | What they receive |
|---|---|---|
| APG2575 + Azacitidine | Experimental | 200 mg APG2575 dose ramp up +AZA Receives: Drug: APG 2575 ramp up arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Dose-limiting toxicity (DLT) rate at each dose level
DLT will be assessed within the first 28-day cycle of study treatment via CTCAE version 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 posted16 Jul 2021
- Study start30 Jul 2021
- Primary completion30 Jul 2024 (estimated)
- Study completion30 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AML, AdultStudies 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
- Not applicable
- Intervention model
- Sequential
- Model description
- 3+3 dose escalation
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Qian Niu, MD, Principal investigator, Ascentage Pharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04964518
- Sponsor's protocol ID
- APG2575AU101
- Status last verified
- Oct 2023
- First submitted
- 23 Jun 2021
- Last updated
- 25 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML), Mixed Phenotype Acute Leukemia (MPAL), Chronic Myelomonocytic Leukemia (CMML) and Higher-Risk Myelodysplastic Syndrome (MDS
- ClinicalTrials.gov ID
- NCT04964518
- Acronym / sponsor ID
- APG2575AU101
- Conditions
- AML, Adult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Jul 2021 (actual)
- Primary completion
- 30 Jul 2024 (estimated)
- Study completion
- 30 Oct 2024 (estimated)
- First posted
- 16 Jul 2021 (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 Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy and PK of APG-2575 in combination with Azacitidine in the patients with AML/MPAL or MDS/CMML. The study consists of dose escalation (Part I) and dose expansion phase (Part II)
Detailed description
The patients with histologically confirmed relapsed or refractory (R/R) AML/MPAL/CMML or relapsed/refractory Higher-Risk MDS by WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response will be enrolled.
This will be a 3+3 dose escalation to determine the DLTs and MTD/RP2D of APG-2575 (see dose escalation table) given in combination with Azacitidine
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3+3 dose escalation
| Arm | Type | Receives |
|---|---|---|
| APG2575 + Azacitidine | Experimental | Drug: APG 2575 ramp up arm200 mg APG2575 dose ramp up +AZA |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia (AML) or mixed phenotype acute leukemia (MPAL) or Chronic Myelomonocytic Leukemia (CMML) or relapsed/refractory Higher-Risk MDS by 2016 WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response.
- MPAL will include biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population.
- Relapsed/refractory MDS will be defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy with Overall Revised International Prognostic Scoring System (IPSS-R) score > 3 (intermediate, high or very high).
Key exclusion criteria (20 listed)
- Pregnant women.
- 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 within 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 taken strong inhibitors or inducers of CYP3A4 within 7 days prior to the first dose of APG-2575.
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 2575 ramp up armAlso: APG2575APG2575 ramp up + Azacitidine | Drug | APG2575 + Azacitidine |
Primary outcome
DLT
Time frame: 28 days
Dose-limiting toxicity (DLT) rate at each dose level DLT will be assessed within the first 28-day cycle of study treatment via CTCAE version 5.0
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
- Individual participant dataSharing planned: Undecided
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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.
Qian Niu, MD principal investigator
Ascentage Pharma
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APG 2575 ramp up arm in people with AML, Adult, run by Ascentage Pharma Group Inc. at 9 sites in 2 countries.
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 3 inclusion and 20 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 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Australia. 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?
DLT (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 25 Oct 2023.