MDSPhase 1NCT04638309
APR-548 in Combination With Azacitidine for the Treatment of TP53 Myelodysplastic Syndromes (MDS)
A Phase 1 study testing APR-548 + Azacitidine in people with MDS and Myelodysplastic Syndromes, run by Aprea Therapeutics at 4 sites in United States.
Trial summary
Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MDS, Myelodysplastic Syndromes
- What is being tested?
- APR-548 + Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 4 sitesUnited States
- Study dates
- 20 Sep 2021to 25 Apr 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
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
- Adequate organ function as defined by the following laboratory values:
- Creatinine clearance ≥60 mL/min (by Cockcroft-Gault method, Appendix I),
- Total serum bilirubin ≤1.5 × upper limit of normal (ULN) unless due to Gilbert's syndrome or MDS organ involvement,
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN, unless due to MDS organ involvement.
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- Age ≥18 years at the time of signing the informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
- Projected life expectancy of ≥12 weeks.
- Clear ocular media and adequate pupil dilation to permit fundus examination and retinal imaging.
Who cannot join
- Cardiac abnormalities, which includes, but not limited to:
- Myocardial infarction within six months prior to enrollment
- New York Heart Association Class III or IV heart failure or known LVEF <40%
- Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
- Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.
- Prior exposure to eprenetapopt (APR-246).
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- A female subject who is pregnant or breast-feeding.
- Known history of human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
- Malabsorption syndrome or other condition likely to affect gastrointestinal absorption of APR-548.
- Known history or current evidence of ocular disease in either eye
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institue
Boston, Massachusetts, 02215
MD Anderson Cancer Center
Houston, Texas, 77030
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Phase 1 Study to Evaluate Safety and Efficacy of APR-548 in Combination With Azacitidine for the Treatment of TP53-Mutant Myelodysplastic Syndromes
Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.
Read the detailed description
Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).
- Conditions
- MDS, Myelodysplastic Syndromes
- Being tested
- APR-548 + Azacitidine
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APR-548 + AzacitidineDrug
APR-548 monotherapy period followed by APR-548 in combination with Azacitidine
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Dose level 1 Receives: Drug: APR-548 + Azacitidine |
| Cohort 2 | Experimental | Dose level 2 Receives: Drug: APR-548 + Azacitidine |
| Cohort 3 | Experimental | Dose level 3 Receives: Drug: APR-548 + Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Investigate the "Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine
Occurrence of frequency of treatment emergent adverse events by reviewing safety data including AEs, vital signs, laboratory data, ECG, ophthalmologic assessment findings, and other physical exam findings.
Measured: Through study completion, approximately 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2020
- Study start20 Sep 2021
- Primary completion25 Apr 2022
- Study completion25 Apr 2022
Why it stopped: Sponsor decision
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.
- Other trials for MDSStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aprea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joachim Gullbo, MD, Study director, Theradex Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04638309
- Sponsor's protocol ID
- A20-11202
- Status last verified
- Mar 2025
- First submitted
- 13 Nov 2020
- Last updated
- 10 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 10 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study to Evaluate Safety and Efficacy of APR-548 in Combination With Azacitidine for the Treatment of TP53-Mutant Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT04638309
- Acronym / sponsor ID
- A20-11202
- Conditions
- MDS, Myelodysplastic Syndromes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Aprea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 20 Sep 2021 (actual)
- Primary completion
- 25 Apr 2022 (actual)
- Study completion
- 25 Apr 2022 (actual)
- First posted
- 20 Nov 2020 (actual)
- Results
- Posted 7 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1 study evaluating the safety and efficacy of APR-548 in combination with Azacitidine for the treatment of TP53-Mutant Myelodysplastic Syndromes.
Detailed description
Open-label first-in-human (FIH) phase 1 clinical trial assessing the safety, pharmacokinetics (PK), and clinical activity of orally (p.o.) administered APR-548 alone and in combination with azacitidine for the treatment of TP53-mutant myelodysplastic syndromes (MDS).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: APR-548 + AzacitidineDose level 1 |
| Cohort 2 | Experimental | Drug: APR-548 + AzacitidineDose level 2 |
| Cohort 3 | Experimental | Drug: APR-548 + AzacitidineDose level 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Documented diagnosis of TP53-mutant MDS, according to WHO criteria that is relapsed/refractory or previously untreated MDS.
- Adequate organ function as defined by the following laboratory values:
- Age ≥18 years at the time of signing the informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Appendix II).
Key exclusion criteria (10 listed)
- Cardiac abnormalities, which includes, but not limited to:
- Concomitant malignancies or previous malignancies with less than a 1 year disease-free interval at the time of signing informed consent.
- Use of cytotoxic chemotherapeutic agents, or experimental agents for the treatment of MDS within 14 days or 5 half-lives of the product (whichever is shorter) of the first day of study drug treatment.
- Prior exposure to eprenetapopt (APR-246).
- A female subject who is pregnant or breast-feeding.
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-548 + AzacitidineAPR-548 monotherapy period followed by APR-548 in combination with Azacitidine | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
To Investigate the "Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine
Time frame: Through study completion, approximately 28 days
Occurrence of frequency of treatment emergent adverse events by reviewing safety data including AEs, vital signs, laboratory data, ECG, ophthalmologic assessment findings, and other physical exam findings.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Joachim Gullbo, MD study director
Theradex Oncology
4 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-548 + Azacitidine in people with MDS and Myelodysplastic Syndromes, run by Aprea Therapeutics at 4 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 10 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: stopped early, as of the sponsor's last update on 10 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 4 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 7 Mar 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 Investigate the "Number of Participants With Treatment Emergent Adverse Events From Treatment With APR-548 as Monotherapy and in Combination With Azacitidine (time frame: Through study completion, approximately 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 10 Mar 2025.