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

Trial Status: Active

This phase I trial studies the side effects of ONC 201 as maintenance therapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome after receiving a donor stem cell transplant. ONC 201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • A history of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The patients should have either complex karyotype with >= 3 changes, transplant being performed in second remission or beyond, AML with high-risk mutations (TP53, RUNX1, or ASXL1 mutations), AML with active disease or minimal residual disease positivity before or after transplant, high-risk or very high-risk MDS not responding to 4 cycles of hypomethylating agents, or MDS progressing following initial response
  • Receipt of allogeneic hematopoietic stem cell transplant 6-12 weeks prior to enrollment
  • Disease status: < 5% bone marrow blast at the time of enrollment
  • All donor sources and conditioning regimens are allowed
  • Eastern Cooperative Oncology Group performance status of 0-2
  • Absolute neutrophil count (ANC) greater than 1500/uL
  • Platelet count >= 100,000/uL without the use of growth factors or 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 immunosuppressive agent within 4 weeks prior to enrollment
  • 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


University of Nebraska Medical Center
Status: ACTIVE
Contact: Vijaya Raj Bhatt
Phone: 402-559-8008


I. To determine the rate of dose limiting toxicities during the first cycle (among the dose escalating cohort) and grade >= 3 toxicities during the first 3 cycles of using Akt/ERK inhibitor ONC201 (ONC 201) after an allogeneic hematopoietic stem cell transplant.


I. To identify the rate of toxicities (all grades) associated with the use of ONC 201 during the entire duration of maintenance therapy with ONC 201.

II. To calculate the rate of interruption and cessation of ONC 201 maintenance therapy after an allogeneic hematopoietic stem cell transplant.

III. To explore changes in quality of life associated with the use of ONC 201 after an allogeneic hematopoietic stem cell transplant.

IV. To investigate the impact of ONC 201 on reconstitution of natural killer (NK) and other immune cells.

V. To determine the rate of relapse and relapse-free survival at 1 year and 2 years from the time of enrollment.

VI. To calculate the rate of overall survival and non-relapse mortality at 1 year and 2 years from the time of enrollment.


I. To investigate changes in functional status associated with the use of ONC 201 after an allogeneic stem cell transplant (alloSCT).

II. To determine the rate of clearance of minimal residual disease from baseline to 3 months and 1 year after initiation of therapy.


Patients receive Akt/ERK inhibitor ONC201 orally (PO) once per week. Treatment repeats every 4 weeks for up to 13 cycles (52 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30-40 days and then every 4 months for up to 2 years from the time of enrollment.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Nebraska Medical Center

Principal Investigator
Vijaya Raj Bhatt

  • Primary ID 274-19
  • Secondary IDs NCI-2019-05125
  • ID NCT03932643