Acute Myeloid LeukemiaPhase 1NCT03932643
ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant
A Phase 1 study testing ONC-201 in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Nebraska at 1 site in United States.
Trial summary
This is a single-center Phase 1 trial of 20 patients with AML/MDS. Eligible patients will be enrolled following an informed consent between 6-20 weeks after allogeneic hematopoietic stem cell transplant. Patients will receive weekly oral ONC 201 for a total of 52 weeks. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- ONC-201
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2019to 27 Mar 2025
- Phase
- Phase 1
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A history of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) with at least one of the following features:
- AML: High-risk AML as defined by the 2017 European LeukemiaNet criteria (e.g. complex karyotype with ≥3 changes), AML with high-risk mutations (e.g. TP53, RUNX1, or ASXL1 mutations), transplant being performed in second remission or beyond, or AML with active disease or minimal residual disease positivity before or after transplant.
- MDS: MDS with high or very-high risk cytogenetic changes as defined by the Revised International Prognostic Scoring System (e.g. complex karyotype with ≥3 changes),53 the presence of TP53 mutation, high-risk or very high-risk MDS not responding to 4 cycles of hypomethylating agents, MDS progressing following initial response, persistence of MDS after transplant, or transplant being performed in second remission or beyond.
- Receipt of allogeneic hematopoietic stem cell transplant 6-20 weeks prior to enrollment
- Disease status: <5% bone marrow blast at the time of enrollment
- All donor sources and conditioning regimens are allowed
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- Adults, Age ≥19 years (for the state of Nebraska)
- Karnofsky Performance Status (KPS) of ≥70
- Absolute neutrophil count (ANC) greater than 1000/µL without the use of granulocyte colony stimulating factor in the past 2 weeks, and platelet count ≥50,000/µL without platelet transfusion in the past 2 weeks.
- Able to take oral medication.
- Female patient of reproductive potential must have a negative serum or urine pregnancy test ≤7 days prior to starting the study drug.
- Male and female patients of reproductive potential must be willing to avoid pregnancy or fathering children from enrollment to two months after the end of study treatment. This will require either a total abstinence, OR exclusively non-heterosexual activity (when this is in line with the preferred and usual lifestyle of the subject), OR two methods of contraception
- Written informed consent to participate in the study.
Who cannot join
- A history of acute graft-versus-host disease grade III/IV or initiation of any new immunosuppressive agent for treatment of graft-versus-host disease within 4 weeks prior to enrollment. Oral beclomethasone or budesonide, empirically used for possible but not biopsy-proven graft-versus-host disease, will not be considered an exclusion criterion.
- Use of prednisone at a dose of ≥0.25 mg/kg/day (or equivalent dose of another glucocorticoid) at the time of enrollment
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
- Presence of known HIV infection, active hepatitis B or C infection.
- Total bilirubin, aspartate transaminase, alanine transaminase 2 X the upper limit of the normal range. Patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded.
- Creatinine clearance <30 mL/min
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- Presence of uncontrolled cardiopulmonary conditions such as ongoing cardiac arrhythmias, unstable angina or myocardial infarction, New York Heart Association class III/IV congestive heart failure, or severe chronic obstructive pulmonary disease or other pulmonary condition resulting in a requirement of supplemental oxygen or having a resting O2 saturation <90% by pulse oximetry
- Pregnancy or breastfeeding.
- Known hypersensitivity, or intolerance to any of the study medications, or excipients.
- Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
- Patients on dopamine antagonists for treatment of psychotic disorder or Parkinson's disease will be excluded. A brief use of drugs such as clozapine or haloperidol for a few days for treatment of nausea or other indication will not be prohibited. The use of tricyclic antidepressants does not constitute an exclusion criterion.
- Any other condition that is judged by the physician to potentially interfere with compliance to the study protocol or pose a significant risk to the patient.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: A Phase 1 Trial of ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After an Allogeneic Hematopoietic Stem Cell Transplant
This is a single-center Phase 1 trial of 20 patients with AML/MDS. Eligible patients will be enrolled following an informed consent between 6-20 weeks after allogeneic hematopoietic stem cell transplant. Patients will receive weekly oral ONC 201 for a total of 52 weeks.
Read the detailed description
This is a single-center Phase 1 trial of 20 participants with AML/MDS. Eligible participants will be enrolled following an informed consent between 6-20 weeks after allogeneic hematopoietic stem cell transplant. Participants will receive weekly oral ONC-201 for a total of 52 weeks.
The objectives of the study are: 1. To determine the safety and preliminary efficacy of ONC-201 maintenance therapy among participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who undergo allogeneic hematopoietic stem cell transplant.
Participants will be monitored for toxicities (using Common Terminology Criteria for Adverse Events, CTCAE version 5.0), quality of life [Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)], and immunologic changes. We will also examine changes in functional status (Karnofsky Performance Scale (KPS), instrumental activities of daily living and short physical performance battery), rates of disease relapse and mortality.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- ONC-201
- 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.
ONC-201Drug
Also called dordaviprone
ONC-201 Capsules, 125 mg
Oral ONC-201 at various dose levels will be given at weekly intervals for up to 13 cycles (52 weeks); 4-week therapy will be considered 1 cycle.
| Study group | Role | What they receive |
|---|---|---|
| ONC-201 Treatment | Experimental | A 3+3 dose escalation design will be followed. Given the safety profile in prior trials, A dose of 250 mg weekly will be the starting dose. The first 12-15 patients are expected to receive escalating doses of ONC 201, the remaining patients will go on the expansion cohort. Receives: Drug: ONC-201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose limiting toxicities during the first cycle
The rate of dose limiting toxicities during the first cycle (among the dose escalating cohort)
Measured: after one month of treatment
Grade ≥3 toxicities
The number of grade ≥3 toxicities
Measured: during the first 3 cycles of treatment (each cycle is 28 days)
Secondary outcomes (5)
Number of toxicities (all grades) during the duration of maintenance therapy with ONC 201
Number of toxicities (all grades) associated with the use of ONC 201 during the entire duration of maintenance therapy with ONC 201
Measured: Up to 13 months after initiation of ONC 201
The rate of relapse
The rate of relapse
Measured: Up to 2 years after enrollment
The rate of relapse-free survival
The rate of relapse-free survival
Measured: Up to 2 years after enrollment
Rate of overall survival
Overall survival at 1 year and 2 years from the time of enrollment
Measured: Up to 2 years after enrollment
Rate of non-relapse mortality
Non-relapse mortality at 1 year and 2 years from the time of enrollment
Measured: Up to years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start30 Jul 2019
- Primary completion27 Mar 2025
- Study completion27 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vijaya R Bhatt, MBBS, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03932643
- Sponsor's protocol ID
- 0274-19-FB
- Status last verified
- Nov 2025
- First submitted
- 28 Apr 2019
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bhatt VR, Wichman CS, Bouska A, Ellithi M, Haddadin M, Iqbal J, Talmadge JE, Maness LJ, Gundabolu K. Dordaviprone Maintenance After Allogeneic HCT for High-Risk Acute Myeloid Leukemia and Myelodysplastic Neoplasm. Am J Hematol. 2026 Sep;101(9):2288-2296. doi: 10.1002/ajh.70428. Epub 2026 Jun 26.
PubMed 42359621
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After an Allogeneic Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT03932643
- Acronym / sponsor ID
- 0274-19-FB
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 30 Jul 2019 (actual)
- Primary completion
- 27 Mar 2025 (actual)
- Study completion
- 27 Mar 2025 (actual)
- First posted
- 1 May 2019 (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 single-center Phase 1 trial of 20 patients with AML/MDS. Eligible patients will be enrolled following an informed consent between 6-20 weeks after allogeneic hematopoietic stem cell transplant. Patients will receive weekly oral ONC 201 for a total of 52 weeks.
Detailed description
This is a single-center Phase 1 trial of 20 participants with AML/MDS. Eligible participants will be enrolled following an informed consent between 6-20 weeks after allogeneic hematopoietic stem cell transplant. Participants will receive weekly oral ONC-201 for a total of 52 weeks.
The objectives of the study are: 1. To determine the safety and preliminary efficacy of ONC-201 maintenance therapy among participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who undergo allogeneic hematopoietic stem cell transplant.
Participants will be monitored for toxicities (using Common Terminology Criteria for Adverse Events, CTCAE version 5.0), quality of life [Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)], and immunologic changes. We will also examine changes in functional status (Karnofsky Performance Scale (KPS), instrumental activities of daily living and short physical performance battery), rates of disease relapse and mortality.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ONC-201 Treatment | Experimental | Drug: ONC-201A 3+3 dose escalation design will be followed. Given the safety profile in prior trials, A dose of 250 mg weekly will be the starting dose. The first 12-15 patients are expected to receive escalating doses of ONC 201, the remaining patients will go on the expansion cohort. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- A history of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) with at least one of the following features:
- AML: High-risk AML as defined by the 2017 European LeukemiaNet criteria (e.g. complex karyotype with ≥3 changes), AML with high-risk mutations (e.g. TP53, RUNX1, or ASXL1 mutations), transplant being performed in second remission or beyond, or AML with active disease or minimal residual disease positivity before or after transplant.
- MDS: MDS with high or very-high risk cytogenetic changes as defined by the Revised International Prognostic Scoring System (e.g. complex karyotype with ≥3 changes),53 the presence of TP53 mutation, high-risk or very high-risk MDS not responding to 4 cycles of hypomethylating agents, MDS progressing following initial response, persistence of MDS after transplant, or transplant being performed in second remission or beyond.
- Receipt of allogeneic hematopoietic stem cell transplant 6-20 weeks prior to enrollment
- Disease status: <5% bone marrow blast at the time of enrollment
Key exclusion criteria (12 listed)
- A history of acute graft-versus-host disease grade III/IV or initiation of any new immunosuppressive agent for treatment of graft-versus-host disease within 4 weeks prior to enrollment. Oral beclomethasone or budesonide, empirically used for possible but not biopsy-proven graft-versus-host disease, will not be considered an exclusion criterion.
- Use of prednisone at a dose of ≥0.25 mg/kg/day (or equivalent dose of another glucocorticoid) at the time of enrollment
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
- Presence of known HIV infection, active hepatitis B or C infection.
- Total bilirubin, aspartate transaminase, alanine transaminase 2 X the upper limit of the normal range. Patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded.
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 |
|---|---|---|
| ONC-201Also: dordaviproneONC-201 Capsules, 125 mg Oral ONC-201 at various dose levels will be given at weekly intervals for up to 13 cycles (52 weeks); 4-week therapy will be considered 1 cycle. | Drug | ONC-201 Treatment |
Primary outcome
Rate of dose limiting toxicities during the first cycle
Time frame: after one month of treatment
The rate of dose limiting toxicities during the first cycle (among the dose escalating cohort)
Grade ≥3 toxicities
Time frame: during the first 3 cycles of treatment (each cycle is 28 days)
The number of grade ≥3 toxicities
5 secondary outcomes
Number of toxicities (all grades) during the duration of maintenance therapy with ONC 201
Time frame: Up to 13 months after initiation of ONC 201
The rate of relapse
Time frame: Up to 2 years after enrollment
The rate of relapse-free survival
Time frame: Up to 2 years after enrollment
Rate of overall survival
Time frame: Up to 2 years after enrollment
Rate of non-relapse mortality
Time frame: Up to years after enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Derived from this study: PubMed 42359621Bhatt VR, Wichman CS, Bouska A, Ellithi M, Haddadin M, Iqbal J, Talmadge JE, Maness LJ, Gundabolu K. Dordaviprone Maintenance After Allogeneic HCT for High-Risk Acute Myeloid Leukemia and Myelodysplastic Neoplasm. Am J Hematol. 2026 Sep;101(9):2288-2296. doi: 10.1002/ajh.70428. Epub 2026 Jun 26.
- 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.
Vijaya R Bhatt, MBBS principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ONC-201 in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Nebraska at 1 site 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 12 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 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Rate of dose limiting toxicities during the first cycle (time frame: after one month of treatment). 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 NCT03932643, 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 28 May 2026.