ONC201 Maintenance Therapy for Acute Myeloid Leukemia

Overseen By Marnee B Strege, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Nebraska

Must not be taking: Dopamine antagonists

Disqualifiers: HIV, Hepatitis B/C, Cardiopulmonary, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ONC201 as a maintenance therapy for individuals with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who recently underwent a stem cell transplant. The goal is to assess ONC201's effectiveness and safety when taken weekly for a year. Participants should have a history of AML or MDS, have received a stem cell transplant 6 to 20 weeks prior, and currently have their disease under control. The study seeks patients who can take oral medication and are not experiencing severe infections or other major health issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain medications like high-dose prednisone or dopamine antagonists for psychotic disorders or Parkinson's disease. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ONC201 is likely to be safe for humans?

Research has shown that ONC201 was well-tolerated in earlier studies. For example, patients with certain brain tumors handled ONC201 well, and some experienced lasting positive effects. In early tests with other cancers, such as leukemia, ONC201 stopped or shrank tumors with few side effects.

This trial is in its early stages, and the main goal is to assess the safety of ONC201 for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) after a stem cell transplant. Researchers are closely monitoring how the body processes the drug and are watching for any negative reactions. While the current data is encouraging, more studies are needed to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia that often involve chemotherapy and stem cell transplants, ONC201 offers a novel approach by targeting the DRD2 receptor, a mechanism not typically explored in current therapies. This unique method potentially bypasses the severe side effects associated with traditional chemotherapy. Researchers are particularly excited because this targeted approach might provide a more precise treatment option, potentially improving outcomes while minimizing harm to healthy cells.

What evidence suggests that ONC201 might be an effective treatment for acute myeloid leukemia?

Research has shown that ONC201, the investigational treatment in this trial, may help treat certain cancers, such as acute myeloid leukemia (AML). Studies have found that ONC201 can induce cancer cell death and inhibit their growth. In cases of acute leukemia, ONC201 proved to be safe and effective, with some trials suggesting it maintains efficacy over time. Participants in other trials tolerated ONC201 well, indicating potential for long-term use. While further research is necessary to confirm these findings, early results are promising for those with AML. ^{1 3 6 7 8}

Who Is on the Research Team?

Vijaya R Bhatt, MBBS

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

Adults over 19 with a history of high-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS), post stem cell transplant, can join this trial. They must have stable blood counts, be able to take oral meds, and not be pregnant or planning pregnancy. Exclusions include severe organ dysfunction, uncontrolled infections or heart/lung conditions, certain drug sensitivities, and recent graft-versus-host disease.

Inclusion Criteria

My white blood cell and platelet counts are within safe ranges without recent medical help.

I have a history of AML or MDS.

My bone marrow has less than 5% cancer cells.

Exclusion Criteria

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.

I am currently taking a high dose of prednisone or a similar medication.

My liver tests are within twice the normal limit, except for high bilirubin due to Gilbert syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly oral ONC-201 for a total of 52 weeks

52 weeks

Follow-up

Participants are monitored for safety, effectiveness, and relapse-free survival after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• ONC201

Trial Overview The study tests ONC201 as maintenance therapy for AML/MDS patients after a stem cell transplant. It's an oral medication taken weekly for one year to see if it helps prevent cancer from returning.

How Is the Trial Designed?

Group I: ONC-201 Treatment Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Vijaya Bhatt

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Recent studies indicate that maintenance therapy for acute myeloid leukemia (AML) can be beneficial, particularly for high-risk patients or those with measurable residual disease (MRD), as shown in randomized trials.

The introduction of modern targeted agents, such as oral hypomethylating agents and immune checkpoint inhibitors, has renewed interest in maintenance therapy, emphasizing the need for standardized MRD measurement techniques in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Shallis, RM., Podoltsev, NA.[2023]

Since 2017, the FDA has approved nine new agents for treating acute myeloid leukemia (AML), marking significant progress in AML therapy after decades of slow advancement.

Specific treatments for subsets of AML, such as all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia, have led to impressive 10-year survival rates of over 80%, demonstrating the efficacy of targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. Kantarjian, HM., Kadia, TM., DiNardo, CD., et al.[2021]

Citations

1. researchgate.net researchgate.net/publication/292967907_Caspase-Dependent_Anti-Tumor_Effects_of_ONC201TIC10_on_Acute_Myeloid_Leukemia_AML_and_Multiple_Myeloma_MM

Caspase-Dependent Anti-Tumor Effects of ONC201/TIC10 ... Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7588802/

ONC201 and imipridones: Anti-cancer compounds with ... ONC201 exhibited time- and dose-dependent pro-apoptotic and antiproliferative effects in acute lymphoblastic leukemia (ALL), anaplastic large cell lymphoma ( ...

3. sigma.larvol.com sigma.larvol.com/product.php?e1=3823&tab=newstrac&page=3

Modeyso (dordaviprone) News ONC201 exhibits activity in H3K27M-mutant gliomas irrespective of CNS location. ONC201 monotherapy was well tolerated and exhibited durable and clinically ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02392572

Study Details | NCT02392572 | ONC201 in Treating ... This phase I/II trial studies the side effects and best dose of ONC201 and to see how well it works in treating patients with acute leukemia or high-risk ...

5. stjude.org stjude.org/research/progress/2024/blazing-trail-in-acute-myeloid-leukemia-treatment.html

Blazing a TRAIL in acute myeloid leukemia treatment ONC201 demonstrated good safety and efficacy through phase 2 clinical trials — warranting a deeper understanding of the mechanism by which it ...

6. researchgate.net researchgate.net/publication/336423990_Caspase-Dependent_Anti-Tumor_Effects_of_ONC201TIC10_on_Acute_Myeloid_Leukemia_AML_and_Multiple_Myeloma_MM

Caspase-Dependent Anti-Tumor Effects of ONC201/TIC10 on ... Our work demonstrates activity of ONC201/TIC10 against AML and MM cell lines including fresh AML tumor cells. The efficacy data with resistant cells is in par ...

7. mdpi.com mdpi.com/1467-3045/47/9/775

Combination of the First-in-Class Imipridone ONC201 and ... A phase II clinical study reported on safety and suggested that this drug exerts single-agent activity in recurrent glioblastoma [23]. However, later ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/23/15/4163/257537/First-in-Human-Clinical-Trial-of-Oral-ONC201-in

First-in-Human Clinical Trial of Oral ONC201 in Patients with ... ONC201 has exhibited proapoptotic antitumor effects, manifesting as tumor regressions or stasis, as a single agent with infrequent oral dosing in numerous ...