Using ONC201 to treat patients with relapsed or refractory acute leukemia or high-risk myelodysplastic syndrome
Phase I/II Study of Oral ONC201 in Patients With Relapsed or Refractory Acute Leukemias and High-Risk Myelodysplastic Syndromes
This study is testing if a new drug called ONC201 can help people with relapsed or hard-to-treat acute leukemia or high-risk myelodysplastic syndrome feel better and improve their health.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 120 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | M.D. Anderson Cancer Center Academic / other |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT02392572 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the effectiveness and safety of ONC201, an Akt/ERK inhibitor, in patients with relapsed or refractory acute leukemia or high-risk myelodysplastic syndrome. The study is divided into two phases: the first phase focuses on determining the optimal dose and identifying side effects, while the second phase assesses the treatment's effectiveness. Patients will receive ONC201 alone or in combination with Venetoclax, and various clinical outcomes will be monitored, including response rates and pharmacokinetics.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory acute leukemias or high-risk myelodysplastic syndrome who have no standard therapies available.
Not a fit: Patients who are pregnant, nursing, or have standard treatment options that could lead to a durable remission may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat forms of leukemia and myelodysplastic syndrome.
How similar studies have performed: Other studies have shown promise with similar approaches using Akt/ERK inhibitors, but this specific combination is being evaluated for the first time.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * For Arms A, B, C, D, E, F patients must have relapsed or refractory acute leukemias or high-risk MDS for which no standard therapies are anticipated to result in a durable remission * Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device, such as a condom, diaphragm, or cervical/vault cap), for 16 weeks after the last dose of study drug, and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial; nursing patients are excluded; sexually active men must also use acceptable contraceptive methods for the duration of time on study and for at least 16 weeks after the last dose of study drug; pregnant and nursing patients are excluded because the effects of ONC201on a fetus or nursing child are unknown * Must be able and willing to give written informed consent * The interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents; if the patient is on hydroxyurea to control peripheral blood leukemic cell counts, the patient must be off hydroxyurea for at least 24 hours before initiation of treatment on this protocol; persistent clinically significant toxicities from prior therapy must not be greater than grade 1 * Serum creatinine \< 2.0 mg/dl * Total bilirubin =\< 1.5 x the upper limit of normal (ULN) unless considered due to Gilbert's syndrome * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =\< 3 x the ULN unless considered due to organ leukemic involvement * Relapse \> 6 months since autologous or allogeneic stem cell transplantation provided: * No active graft-versus-host disease (GVHD \> grade 1) * No treatment with high dose steroids for GVHD (up to \>= 20 mg prednisolone or equivalent per day) * No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus Exclusion Criteria: * Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (New York Heart Association class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure (New York Heart Association class III and IV) * Patients receiving any other standard or investigational treatment for their hematologic malignancy within past 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents * Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy * Known history of seropositive for human immunodeficiency virus (HIV) antibodies (HIV1 and HIV2), hepatitis C antibody (Hep C Ab) or a hepatitis B carrier (positive for hepatitis B surface antigen \[HBsAg\]) * Active drug use or alcoholism * Known or active central nervous system (CNS) involvement by leukemia * White blood cell count more than 25 x 109/L prior to initiation of venetoclax
Where this trial is running
Houston, Texas
- M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Gautam Borthakur — M.D. Anderson Cancer Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.