MDSPhase 3NCT03745716
APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)
A Phase 3 study testing APR-246 + azacitidine and Azacitidine in people with MDS, run by Aprea Therapeutics at 27 sites in 2 countries.
Trial summary
A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MDS
- What is being tested?
- APR-246 + azacitidine and Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 154 participants
- Where
- 27 sitesin 2 countries
- Study dates
- 11 Jan 2019to 14 Jan 2022
- Phase
- Phase 3
- 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 (ICF) and is able to comply with protocol requirements
- Documented diagnosis of MDS, according to World Health Organization (WHO) classification
- Patient has adequate organ function as defined by the following laboratory values:
- Creatinine clearance > 30 mL/min (by Cockcroft-Gault method)
- Total serum bilirubin < 1.5 x Upper Limit of Normal (ULN) or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome or hemolysis or who required regular blood transfusions
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN
Show all 11Show fewer
- Age ≥18 years at the time of signing the informed consent form (ICF)
- Having at least one TP53 mutation which is not benign or likely benign
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- If of childbearing potential, negative pre-treatment urine or serum pregnancy test
- If of childbearing potential (males and females), willing to use an effective form of contraception such as latex condom, hormonal birth control, intrauterine device or double barrier method during chemotherapy treatment and for at least six months thereafter
Who cannot join
- Patient has a known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory)
- Patient has any of the following cardiac abnormalities (as determined by treating MD):
- Myocardial infarct within six months prior to registration,
- New York Heart Association Class II or worse heart failure (Appendix II) or known left ventricular ejection fraction (LVEF) < the institution lower limit of normal as assessed by echocardiogram
- A history of familial long QT syndrome,
- Clinically significant pericardial disease
Show all 18Show fewer
- Electrocardiographic evidence of acute ischemia
- Symptomatic atrial or ventricular arrhythmias not controlled by medications
- QTc ≥ 470 msec (QT cardiac interval)
- Bradycardia (<40 bpm)
- Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis
- Prior exposure to azacitidine, decitabine or investigational hypomethylating agent
- Prior exposure to intensive chemotherapy
- Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment
- No concurrent use of erythroid stimulating agents
- Patients with history of allogeneic stem cell transplantation
- Pregnant women are excluded from this study because APR-246 has not been studied in pregnant patients. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with APR 246, breastfeeding should be discontinued if the mother is treated with APR-246.
- Patients with active uncontrolled infections
Trial locations and contacts
27 sites in 2 countries.
27 sites in 2 countries
United States23 sites
Johns Hopkins Medical Center
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Robert H Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, 60611
University Of Chicago Medicine
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
City of Hope
Duarte, California, 91010
Memorial Health Care System South Florida
Hollywood, Florida, 33021
MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa Hospitals and Clinics, Holden Cancer Center
Iowa City, Iowa, 52242
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Yale Cancer Center
New Haven, Connecticut, 06510
Ochsner Cancer Institute
New Orleans, Louisiana, 70121
Cornell Medical Center
New York, New York, 10065
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stanford University Cancer Research Center
Palo Alto, California, 94304
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center, Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Mayo Clinic Rochester
Rochester, Minnesota, 55902
Fred Hutchinson Cancer Research Center
Seattle, Washington, 19023
Washington University St. Louis
St Louis, Missouri, 63130
Moffitt Cancer Center
Tampa, Florida, 12902
France4 sites
CHU Nantes
Nantes, 44093
CHU Nice
Nice, 06000
Hôpital Saint-Louis
Paris, 75010
IUCT Oncopole
Toulouse, 31100
About this study
Official title: A Phase III Multicenter, Randomized, Open Label Study of APR-246 in Combination With Azacitidine Versus Azacitidine Alone for the Treatment of (Tumor Protein) TP53 Mutant Myelodysplastic Syndromes
A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Read the detailed description
A Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease.
Patients will be randomized (1:1) to one of two arms:
- Experimental arm: APR-246 + azacitidine; or
- Control arm: Azacitidine
- Conditions
- MDS
- Being tested
- APR-246 + azacitidine, Azacitidine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APR-246 + azacitidineDrug
Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):
Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine
AzacitidineDrug
Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65):
Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm: APR-246 + azacitidine | Experimental | Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): Receives: Drug: APR-246 + azacitidine |
| Control arm: Azacitidine | Experimental | Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate (CR)
To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR) with APR 246 + azacitidine treatment vs. azacitidine only.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start11 Jan 2019
- Primary completion27 Nov 2020
- 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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This will be a Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone. Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease. Patients will be randomized (1:1) to one of two arms: stratified by age (\< 65 years versus ≥ 65): * Experimental arm: APR-246 + azacitidine; or * Control arm: Azacitidine
- Masking
- None (open label)
- Enrolment
- 154 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aprea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Sallman, MD, PhD, Principal investigator, Moffitt Cancer Center, Tampa, US
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03745716
- Sponsor's protocol ID
- A18-15331
- Status last verified
- Mar 2025
- First submitted
- 14 Nov 2018
- Last updated
- 18 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Multicenter, Randomized, Open Label Study of APR-246 in Combination With Azacitidine Versus Azacitidine Alone for the Treatment of (Tumor Protein) TP53 Mutant Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT03745716
- Acronym / sponsor ID
- A18-15331
- Conditions
- MDS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 154 participants (actual)
- Lead sponsor
- Aprea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 11 Jan 2019 (actual)
- Primary completion
- 27 Nov 2020 (actual)
- Study completion
- 14 Jan 2022 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Posted 12 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase III, multicenter, randomized study to compare the rate of complete response (CR) and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Detailed description
A Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone.
Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease.
Patients will be randomized (1:1) to one of two arms:
- Experimental arm: APR-246 + azacitidine; or
- Control arm: Azacitidine
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This will be a Phase III, multicenter, randomized study to compare the rate of CR and duration of CR, in patients with TP53-mutated MDS who will receive APR-246 and azacitidine or azacitidine alone. Treatment will be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's disease. Patients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): * Experimental arm: APR-246 + azacitidine; or * Control arm: Azacitidine
| Arm | Type | Receives |
|---|---|---|
| Experimental arm: APR-246 + azacitidine | Experimental | Drug: APR-246 + azacitidinePatients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): |
| Control arm: Azacitidine | Experimental | Drug: AzacitidinePatients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed Informed Consent (ICF) and is able to comply with protocol requirements
- Documented diagnosis of MDS, according to World Health Organization (WHO) classification
- Patient has adequate organ function as defined by the following laboratory values:
- Age ≥18 years at the time of signing the informed consent form (ICF)
- Having at least one TP53 mutation which is not benign or likely benign
Key exclusion criteria (18 listed)
- Patient has a known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory)
- Patient has any of the following cardiac abnormalities (as determined by treating MD):
- Concomitant malignancies or previous malignancies with less than a 1-year disease free interval at the time of signing consent. Patients with adequately resected basal or squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g. cervix) may enroll irrespective of the time of diagnosis
- Prior exposure to azacitidine, decitabine or investigational hypomethylating agent
- Prior exposure to intensive chemotherapy
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-246 + azacitidinePatients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine | Drug | Experimental arm: APR-246 + azacitidine |
| AzacitidinePatients will be randomized (1:1) to one of two arms: stratified by age (< 65 years versus ≥ 65): Experimental arm: APR-246 + azacitidine; or Control arm: Azacitidine | Drug | Control arm: Azacitidine |
Primary outcome
Complete Response Rate (CR)
Time frame: 12 months
To compare the complete response rate, defined as the proportion of patients who achieve complete remission (CR) with APR 246 + azacitidine treatment vs. azacitidine only.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for MDS
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
David Sallman, MD, PhD principal investigator
Moffitt Cancer Center, Tampa, US
27 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing APR-246 + azacitidine and Azacitidine in people with MDS, run by Aprea Therapeutics at 27 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 11 inclusion and 18 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 18 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 27 sites in United States, France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 12 Jul 2022). 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?
Complete Response Rate (CR) (time frame: 12 months). 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 18 Mar 2025.