120 Participants Needed

ONC201 for Leukemia

Recruiting at 1 trial location
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

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 myelodysplastic syndrome that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). ONC201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking any standard or investigational treatments for your blood cancer at least 2 weeks before starting the study drug. If you're taking hydroxyurea, you must stop it at least 24 hours before starting the trial. The protocol does not specify other medications, but you should discuss your current medications with the trial team.

What makes the drug ONC201 unique for treating leukemia?

ONC201 is unique because it targets a specific pathway in cancer cells, potentially offering a new approach for treating leukemia compared to traditional therapies. While other treatments like histone deacetylase inhibitors focus on altering gene expression, ONC201 works through a different mechanism, which may provide benefits in cases where other treatments are less effective.12345

Who Is on the Research Team?

Gautam Borthakur | MD Anderson Cancer ...

Gautam Borthakur, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with acute leukemia or high-risk myelodysplastic syndrome that's relapsed or refractory. They must be in fair health (ECOG 0-2), able to consent, and have no severe persistent side effects from past treatments. No recent heart issues, other cancer treatments within 3 years (except certain low-risk cases), or active infections like HIV/Hepatitis B/C.

Inclusion Criteria

ALT or AST =< 3 x the ULN unless considered due to organ leukemic involvement
Must be able and willing to give written informed consent
Serum creatinine < 2.0 mg/dl
See 6 more

Exclusion Criteria

Known history of seropositive for HIV antibodies, hepatitis C antibody, or a hepatitis B carrier
Active drug use or alcoholism
I do not have any unmanaged ongoing illnesses.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Akt/ERK inhibitor ONC201 orally in various dosing schedules depending on the assigned arm. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.

63 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • ONC201
Trial Overview The trial is testing ONC201, a drug thought to block enzymes that cancer cells need to grow. It aims to find the safest dose and see how effective it is for patients whose disease has returned after treatment or hasn't responded at all.
How Is the Trial Designed?
5Treatment groups
Experimental Treatment
Group I: Arm E (Akt/ERK inhibitor ONC201)Experimental Treatment2 Interventions
Arm E (Akt/ERK inhibitor ONC201) Patients receive Akt/ERK inhibitor ONC201 PO twice weekly for 4 weeks and venetoclax daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II: Arm D (Akt/ERK inhibitor ONC201)Experimental Treatment2 Interventions
Patients receive Akt/ERK inhibitor ONC201 PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group III: Arm C (Akt/ERK inhibitor ONC201)Experimental Treatment2 Interventions
Patients receive Akt/ERK inhibitor ONC201 PO on the first two consecutive days of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group IV: Arm B (Akt/ERK inhibitor ONC201)Experimental Treatment2 Interventions
Patients receive Akt/ERK inhibitor ONC201 PO once every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Group V: Arm A (Akt/ERK inhibitor ONC201)Experimental Treatment2 Interventions
Patients receive Akt/ERK inhibitor ONC201 PO once every 3 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Oncoceutics, Inc.

Industry Sponsor

Trials
10
Recruited
500+

Published Research Related to This Trial

The deacetylase inhibitor LAQ824 causes significant apoptosis in acute myeloid leukemia progenitor cells (AML-PC) and inhibits their ability to grow again, unlike the DACi valproic acid which does not have this effect.
LAQ824 also affects normal hematopoietic progenitor cells (HPC) by causing cell cycle arrest and apoptosis, particularly in committed HPC, while inducing changes in gene expression related to the notch pathway, which may explain its reversible hematotoxicity.
The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic progenitor cells.Schwarz, K., Romanski, A., Puccetti, E., et al.[2010]
SK-7041, a novel histone deacetylase inhibitor, effectively inhibits the growth of chronic myeloid leukemia cells by altering key cell cycle regulators and activating apoptosis pathways.
When combined with STI571, SK-7041 enhances the treatment's effectiveness against chronic myeloid leukemia, suggesting it could help overcome resistance to STI571 in patients.
Combination of SK-7041, one of novel histone deacetylase inhibitors, and STI571-induced synergistic apoptosis in chronic myeloid leukemia.Kim, BS., Bae, E., Kim, YJ., et al.[2015]
The combination of the liposomal ATRA analog ATRA-IV and divalproex sodium was tested in a phase I trial involving nine patients with advanced solid tumors, showing manageable side effects like skin toxicity and thrombocytopenia, all rated as grade 2 or lower.
Although the trial could not determine the maximum tolerated dose due to early closure, one patient experienced disease stabilization, indicating potential efficacy of the treatment in this challenging patient population.
Phase I trial of ATRA-IV and Depakote in patients with advanced solid tumor malignancies.David, KA., Mongan, NP., Smith, C., et al.[2020]

Citations

The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic progenitor cells. [2010]
Combination of SK-7041, one of novel histone deacetylase inhibitors, and STI571-induced synergistic apoptosis in chronic myeloid leukemia. [2015]
Phase I trial of ATRA-IV and Depakote in patients with advanced solid tumor malignancies. [2020]
Characteristics of Adult T-Cell Leukemia/Lymphoma Patients with Long Survival: Prognostic Significance of Skin Lesions and Possible Beneficial Role of Valproic Acid. [2020]
Effect of histone deacetylase inhibitors trichostatin A and valproic acid on etoposide-induced apoptosis in leukemia cells. [2013]
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