Myeloid MalignancyPhase 1NCT04214860

APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies

A Phase 1 study testing APR-246, Venetoclax and Azacitidine in people with Myeloid Malignancy, run by Aprea Therapeutics at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This clinical trial is a Phase I, open-label, dose-finding and cohort expansion study to determine the safety and preliminary efficacy of APR-246 in combination with venetoclax and azacitidine in patients with myeloid malignancies. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Myeloid Malignancy
What is being tested?: APR-246, Venetoclax and Azacitidine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 8 sitesUnited States
Study dates: 13 Dec 2019to 14 Jan 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Signed informed consent and ability to comply with protocol requirements.
Documented diagnosis of AML according to World Health Organization WHO) classification
Adequate organ function as defined by the following laboratory values:
Creatinine clearance > 30 mL/min
Total serum bilirubin < 1.5 × ULN
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × ULN

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Age ≥18 years
At least one TP53 mutation
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Projected life expectancy of ≥ 12 weeks.
Negative serum or urine pregnancy test
Females of childbearing potential and males with female partners of childbearing potential must be willing to use an effective form of contraception

Who cannot join

Prior treatment for TP53-mutant AML (*dependent upon treatment arm assigned).
Known history of HIV or active hepatitis B or active hepatitis C infection.
Any of the following cardiac abnormalities:
Myocardial infarction within six months prior to registration;
New York Heart Association Class III or IV heart failure or known left ventricular ejection fraction (LVEF) < 40%;
A history of familial long QT syndrome;

Show all 13Show fewer

Symptomatic atrial or ventricular arrhythmias
QTcF ≥ 470 msec, unless due to underlying bundle branch block and/or pacemaker and with approval of the medical monitor.
Concomitant malignancies for which patients are receiving active therapy
Known active CNS involvement from AML.
Malabsorption syndrome
Pregnancy or lactation.
Active uncontrolled systemic infection (viral, bacterial or fungal).

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United States8 sites

Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Northwestern Medicine
Chicago, Illinois, 60611
University of Chicago Medicine
Chicago, Illinois, 60637
MD Anderson Cancer Center
Houston, Texas, 77030
Yale Cancer Center
New Haven, Connecticut, 06511
Weill Cornell Cancer Center
New York, New York, 10021
Memorial Sloan Kettering CC
New York, New York, 10065
H. Lee Moffitt CC
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Phase I Study of APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies

Read the detailed description

This study will enroll adult male and female patients of age ≥ 18 years with documented diagnosis of AML, according to WHO classification, and documented TP53 mutation which is not benign or likely benign, who also meet the eligibility requirements of this protocol.

The study will include a safety lead-in dose-finding portion followed by expansion portion. During the safety lead-in portion of the study, two cohorts will independently enroll patients following a 3 + 3 design. Each cohort will enroll up to 6 patients.

The expansion portion will begin once the recommended phase II dose (RP2D) of APR-246 in combination with venetoclax and in combination with venetoclax and azacitidine have been determined in order to assess the antitumor activity of these combinations.

Conditions: Myeloid Malignancy
Being tested: APR-246, Venetoclax, Azacitidine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

APR-246Drug
APR-246 4.5 g/day
VenetoclaxDrug
Venetoclax 400 mg once daily
AzacitidineDrug
Subcutaneous injection, or intravenous infusion

Study groups in NCT04214860
Study group	Role	What they receive
APR-246	Experimental	APR-246 4.5 g/day Receives: Drug: APR-246; Drug: Venetoclax; Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.
1. Dose-limiting toxicities (DLTs), classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).
Measured: From baseline until event occures, i.e. through study completion, an average of 1 year
To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.
1. Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with venetoclax and azacitidine during the trial.
Measured: From baseline until event occures, i.e. through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Dec 201914 Jan 2022

First posted2 Jan 2020
Study start13 Dec 2019
Primary completion14 Jan 2022
Study completion14 Jan 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Myeloid MalignancyStudies of the same condition, open and under way.
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: Not applicable
Intervention model: Sequential
Model description: The study will include a safety lead-in dose-finding portion followed by the expansion portion. During the safety lead-in portion of the study, two cohorts will independently enroll patients following a 3 + 3 design.
Masking: None (open label)
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04214860
Sponsor's protocol ID: A19-11184
Status last verified: Mar 2025
First submitted: 12 Dec 2019
Last updated: 17 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Garcia-Manero G, Goldberg AD, Winer ES, Altman JK, Fathi AT, Odenike O, Roboz GJ, Sweet K, Miller C, Wennborg A, Hickman DK, Kanagal-Shamanna R, Kantarjian H, Lancet J, Komrokji R, Attar EC, Sallman DA. Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. Lancet Haematol. 2023 Apr;10(4):e272-e283. doi: 10.1016/S2352-3026(22)00403-3.
PubMed 36990622

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Myeloid Malignancy trials

Study at a glance

From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study of APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies
ClinicalTrials.gov ID: NCT04214860
Acronym / sponsor ID: A19-11184
Conditions: Myeloid Malignancy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: Aprea TherapeuticsIndustry (pharma, biotech, devices)
Study start: 13 Dec 2019 (actual)
Primary completion: 14 Jan 2022 (actual)
Study completion: 14 Jan 2022 (actual)
First posted: 2 Jan 2020 (actual)
Results: Posted 21 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: The study will include a safety lead-in dose-finding portion followed by the expansion portion. During the safety lead-in portion of the study, two cohorts will independently enroll patients following a 3 + 3 design.

Arm	Type	Receives
APR-246	Experimental	Drug: APR-246, Drug: Venetoclax, Drug: AzacitidineAPR-246 4.5 g/day

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Signed informed consent and ability to comply with protocol requirements.
Documented diagnosis of AML according to World Health Organization WHO) classification
Adequate organ function as defined by the following laboratory values:
Age ≥18 years
At least one TP53 mutation

Key exclusion criteria (13 listed)

Prior treatment for TP53-mutant AML (*dependent upon treatment arm assigned).
Known history of HIV or active hepatitis B or active hepatitis C infection.
Any of the following cardiac abnormalities:
Concomitant malignancies for which patients are receiving active therapy
Known active CNS involvement from AML.

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
APR-246APR-246 4.5 g/day	Drug	APR-246
VenetoclaxVenetoclax 400 mg once daily	Drug	APR-246
AzacitidineSubcutaneous injection, or intravenous infusion	Drug	APR-246

Primary outcome

To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.
Time frame: From baseline until event occures, i.e. through study completion, an average of 1 year
1. Dose-limiting toxicities (DLTs), classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0).
To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.
Time frame: From baseline until event occures, i.e. through study completion, an average of 1 year
2. Frequency of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) related to APR-246 in combination with venetoclax and azacitidine during the trial.

Results and safety

Results posted to the registry on 21 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1	6	6
Cohort 2	45	43

Primary outcome: To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.

Time frame: From baseline until event occures, i.e. through study completion, an average of 1 year. Number. Unit: DLTs

Measure	Cohort 1 n = 6	Cohort 2 n = 43
Value	0	0

Primary outcome: To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies.

Time frame: From baseline until event occures, i.e. through study completion, an average of 1 year. Count of participants. Unit: Participants

Measure	Cohort 1 n = 6	Cohort 2 n = 43
Value	5	32

Population analysed: Any Serious TEAEs

Adverse events

Time frame: 18 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1	5 of 6 (83.3%)	6 of 6 (100%)	6 of 6
Cohort 2	32 of 43 (74.4%)	43 of 43 (100%)	26 of 43

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36990622Garcia-Manero G, Goldberg AD, Winer ES, Altman JK, Fathi AT, Odenike O, Roboz GJ, Sweet K, Miller C, Wennborg A, Hickman DK, Kanagal-Shamanna R, Kantarjian H, Lancet J, Komrokji R, Attar EC, Sallman DA. Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study. Lancet Haematol. 2023 Apr;10(4):e272-e283. doi: 10.1016/S2352-3026(22)00403-3.
Individual participant dataSharing planned: No

Related trials for Myeloid Malignancy

RecruitingPhase 1
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AML (Acute Myeloid Leukemia)
RecruitingPhase 1
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RecruitingPhase 1
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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.

The record lists no contact. Use the official record to reach the sponsor.

8 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 APR-246, Venetoclax and Azacitidine in people with Myeloid Malignancy, run by Aprea Therapeutics 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 12 inclusion and 13 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: finished, as of the sponsor's last update on 17 Mar 2025. 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 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?

Yes. Results are posted in the registry (first posted 21 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To Evaluate the Tolerabililty and the Incidence of Treatment-Emergent Adverse Events of Administration of APR 246 in Combination With Venetoclax and Azacitidine in Patients With TP53 Mutant Myeloid Malignancies. (time frame: From baseline until event occures, i.e. through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04214860, which also lists 1 linked publication.

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 17 Mar 2025.