ONC 201 Maintenance Therapy for the Treatment of Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome after Donor Stem Cell Transplant

Inclusion Criteria

• 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, or secondary-type mutations), patients who require ≥ 2 induction or lines of therapy to achieve complete remission, secondary or treatment-related AML except for those considered good-risk by the 2017 European LeukemiaNet criteria, 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 used in the Revised International Prognostic Scoring System (e.g. complex karyotype with >= 3 changes), the presence of TP53 mutation, secondary or treatment-related MDS with intermediate or higher-risk cytogenetic changes, MDS with intermediate or higher-risk cytogenetic changes and higher-risk mutations such as EZH2, RUNX1, or ASXL1, 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
• Adults, Age ≥ 19 years (for the state of Nebraska)
• Karnofsky performance status (KPS) of >= 70
• Absolute neutrophil count (ANC) greater than 1000/uL without the use of granulocyte colony stimulating factor in the past 2 weeks
• Platelet count >= 50,000/uL 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. Women are considered NOT to have reproductive potential if they have had 12 months of amenorrhea with an appropriate clinical profile (i.e. >= 51 years, history of vasomotor symptoms, OR supportive hormone levels such as low estrogen and high follicle-stimulating hormone levels), OR surgical sterilization
• 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 (male or female condom with or without a spermicidal agent, diaphragm or cervical cap with spermicide, or hormonal based contraception including intrauterine device)
• Written informed consent to participate in the study

Exclusion Criteria

• A history of acute graft-versus-host disease grade III/IV or initiation of any new systemic 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 human immunodeficiency virus (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
• 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 oxygen (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