Acute Myeloid Leukemia or Myelodysplastic SyndromesPhase 2NCT03931291
APR-246 in Combination With Azacitidine for TP53 Mutated AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes) Following Allogeneic Stem Cell Transplant
A Phase 2 study testing APR-246 in people with Acute Myeloid Leukemia or Myelodysplastic Syndromes, run by Aprea Therapeutics at 7 sites in United States.
Trial summary
A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT (hematopoietic stem cell transplant) for patients with TP53 mutant AML or MDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia or Myelodysplastic Syndromes
- What is being tested?
- APR-246
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 7 sitesUnited States
- Study dates
- 16 Sep 2019to 14 Jan 2022
- Phase
- Phase 2
- 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
- Patient must have previously met pre-transplantation eligibility.
- Patient has received an allogeneic transplant for AML or MDS.
- Any standard (non-study) conditioning [MAC (myeloablative conditioning), RIC (reduced intensity conditioning), or NMA (non-myeloablative conditioning)] will be permitted.
- Patient is ≥ 30 days and ≤ 100 days from hematopoietic cell infusion.
- Patient is in complete remission after the transplant and has achieved engraftment. .
- Patients who have developed grades II-IV acute GVHD (graft versus host disease) will be allowed to initiate maintenance therapy based on the following criteria:
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- Females must either:
- Be of non-childbearing potential postmenopausal (defined as at least 1 year without menses) prior to screening, or documented as surgically sterilized (e.g., hysterectomy or tubal ligation) at least 1 month prior to the screening visit Or, if of childbearing potential, Agree not to try to become pregnant during the study and for 6 months after the final study drug administration And have a negative serum pregnancy test at screening And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and throughout the study period and for 6 months after final study drug administration.
- Females must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
- Males (even if surgically sterilized), and their partners who are women of childbearing potential must be using highly effective contraception in addition to a barrier method throughout the study drug treatment period.
- Males must not donate sperm throughout the study drug treatment period.
- Agrees not to participate in another interventional study while on treatment.
- Karnofsky Performance Status 70 or greater is required.
Who cannot join
- Prior participation in an APR-246 study.
- Use of umbilical cord blood donor and stem cell source.
- Patient has uncontrolled infection.
- Use of investigational agent within 14 days of pre-HSCT screening or anytime thereafter.
- Use of hypomethylating agent, cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS or AML within 14 days of the first day of pre-HSCT screening or anytime thereafter.
- Patient has used experimental therapy for acute GVHD at any time post-transplant.
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- Patient requires treatment with supplemental oxygen not including usage of non-invasive CPAP (continuous positive airways pressure) at night.
- Patient has any of the following cardiac abnormalities (as determined by treating physician):
- Myocardial infarct within six months prior to registration
- New York Heart Association Class II or worse heart failure or known LVEF (left ventricular ejection fraction) < the institution LLN (lower limit normal)
- A history of familial long QT syndrome
- Electrocardiographic evidence of acute ischemia at screening
- Symptomatic atrial or ventricular arrhythmias not controlled by medications
- QTc ≥ 470 ms calculated from a mean of 3 ECG (electrocardiogram) readings using Fridericia's correction (QTcF = QT/RR0.33)
- Bradycardia (<40 bpm) at screening
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21278
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase II Trial of APR-246 in Combination With Azacitidine as Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplant
A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT (hematopoietic stem cell transplant) for patients with TP53 mutant AML or MDS.
Read the detailed description
A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT for patients with TP53 mutant AML or MDS.
Patients will be prescreened for TP53 mutant AML or MDS before they have a HSCT. In order to proceed with APR-246 and azacitidine treatment, engraftment must be confirmed between Day 30 to Day 100 post-HSCT.
APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
- Being tested
- APR-246
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APR-246Drug
Also called Azacitidine
APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm: APR-246 + azacitidine | Experimental | APR-246 and azacitidine maintenance therapy will continue for a maximum of 12 cycles Receives: Drug: APR-246 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Assess Relapse-free Survival (RFS) in Patients With TP53 Mutated AML or MDS After Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT).
Relapse-free survival (RFS) at 12 months or longer if data permits. RFS was defined as the time from HCT to relapse after HCT or death, whichever occurred first.
Measured: 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.
- First posted30 Apr 2019
- Study start16 Sep 2019
- Primary completion27 Aug 2021
- 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 Acute Myeloid Leukemia or Myelodysplastic SyndromesStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aprea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Asmita Mishra, MD, PhD, Principal investigator, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03931291
- Sponsor's protocol ID
- A19-11172
- Status last verified
- Mar 2025
- First submitted
- 26 Apr 2019
- Last updated
- 17 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Mishra A, Tamari R, DeZern AE, Byrne MT, Gooptu M, Chen YB, Deeg HJ, Sallman D, Gallacher P, Wennborg A, Hickman DK, Attar EC, Fernandez HF. Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2022 Dec 1;40(34):3985-3993. doi: 10.1200/JCO.22.00181. Epub 2022 Jul 11.
PubMed 35816664
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 II Trial of APR-246 in Combination With Azacitidine as Maintenance Therapy for TP53 Mutated AML or MDS Following Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT03931291
- Acronym / sponsor ID
- A19-11172
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Aprea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 16 Sep 2019 (actual)
- Primary completion
- 27 Aug 2021 (actual)
- Study completion
- 14 Jan 2022 (actual)
- First posted
- 30 Apr 2019 (actual)
- Results
- Posted 26 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT (hematopoietic stem cell transplant) for patients with TP53 mutant AML or MDS.
Detailed description
A multi-center, open label, Phase II clinical trial to assess the safety and efficacy of APR-246 in combination with azacitidine as maintenance therapy after allogeneic HSCT for patients with TP53 mutant AML or MDS.
Patients will be prescreened for TP53 mutant AML or MDS before they have a HSCT. In order to proceed with APR-246 and azacitidine treatment, engraftment must be confirmed between Day 30 to Day 100 post-HSCT.
APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- APR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles.
| Arm | Type | Receives |
|---|---|---|
| Experimental arm: APR-246 + azacitidine | Experimental | Drug: APR-246APR-246 and azacitidine maintenance therapy will continue for a maximum of 12 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patient must have previously met pre-transplantation eligibility.
- Patient has received an allogeneic transplant for AML or MDS.
- Any standard (non-study) conditioning [MAC (myeloablative conditioning), RIC (reduced intensity conditioning), or NMA (non-myeloablative conditioning)] will be permitted.
- Patient is ≥ 30 days and ≤ 100 days from hematopoietic cell infusion.
- Patient is in complete remission after the transplant and has achieved engraftment. .
Key exclusion criteria (15 listed)
- Prior participation in an APR-246 study.
- Use of umbilical cord blood donor and stem cell source.
- Patient has uncontrolled infection.
- Use of investigational agent within 14 days of pre-HSCT screening or anytime thereafter.
- Use of hypomethylating agent, cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS or AML within 14 days of the first day of pre-HSCT screening or anytime thereafter.
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-246Also: AzacitidineAPR-246 will be administered on Days 1-4, with azacitidine on Days 1-5, of every 28 day cycle. Patients may receive a maximum of 12 cycles. | Drug | Experimental arm: APR-246 + azacitidine |
Primary outcome
To Assess Relapse-free Survival (RFS) in Patients With TP53 Mutated AML or MDS After Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT).
Time frame: Through study completion, an average of 1 year
Relapse-free survival (RFS) at 12 months or longer if data permits. RFS was defined as the time from HCT to relapse after HCT or death, whichever occurred first.
Results and safety
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 35816664Mishra A, Tamari R, DeZern AE, Byrne MT, Gooptu M, Chen YB, Deeg HJ, Sallman D, Gallacher P, Wennborg A, Hickman DK, Attar EC, Fernandez HF. Eprenetapopt Plus Azacitidine After Allogeneic Hematopoietic Stem-Cell Transplantation for TP53-Mutant Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2022 Dec 1;40(34):3985-3993. doi: 10.1200/JCO.22.00181. Epub 2022 Jul 11.
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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.
Asmita Mishra, MD, PhD principal investigator
H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing APR-246 in people with Acute Myeloid Leukemia or Myelodysplastic Syndromes, run by Aprea Therapeutics at 7 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 13 inclusion and 15 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 7 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 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?
Yes. Results are posted in the registry (first posted 26 Mar 2024). 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 Assess Relapse-free Survival (RFS) in Patients With TP53 Mutated AML or MDS After Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HSCT). (time frame: Through study completion, an average of 1 year). 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 NCT03931291, 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.