Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: ONC 201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant

Summary: This is a single-center pilot study of 20 patients with AML/MDS. Eligible patients will be enrolled following an informed consent between 6-12 weeks after allogeneic hematopoietic stem cell transplant. Patients will receive weekly oral ONC 201 for a total of 52 weeks.

Detailed description: This is a single-center pilot study of 20 patients with AML/MDS. Eligible patients will be enrolled following an informed consent between 6-12 weeks after allogeneic hematopoietic stem cell transplant. Patients will receive weekly oral ONC 201 for a total of 52 weeks.
  The objectives of the study are: 1. To determine the safety and preliminary efficacy of ONC 201 maintenance therapy among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), who undergo allogeneic hematopoietic stem cell transplant. 2. To investigate the impact of ONC 201 on reconstitution of NK and other immune cells.
  Patients will be monitored for toxicities (using Common Terminology Criteria for Adverse Events, CTCAE version 5.0), quality of life (Functional Assessment of Cancer Therapy-Bone Marrow Transplant, FACT-BMT), and immunologic changes. We will specifically investigate the impact of ONC 201 on reconstitution of NK and other immune cells. We will also examine changes in functional status (Karnofsky Performance Scale, KPS, instrumental activities of daily living and short physical performance battery), rates of disease relapse and mortality.

Eligibility: Inclusion Criteria:
  1. A history of AML or 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.
  2. Receipt of allogeneic hematopoietic stem cell transplant 6-12 weeks prior to enrollment
  3. Disease status: <5% bone marrow blast at the time of enrollment
  4. All donor sources and conditioning regimens are allowed
  5. Adults, Age ≥19 years (for the state of Nebraska)
  6. Eastern Cooperative Oncology Group performance status of 0-2.
  7. Absolute neutrophil count (ANC) greater than 1500/µL, and platelet count ³100,000/µL without the use of growth factors or platelet transfusion in the past 2 weeks.
  8. Able to take oral medication.
  9. Female patient of reproductive potential must have a negative serum or urine pregnancy test ≤7 days prior to starting the study drug.
  10. 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
  11. Written informed consent to participate in the study.
  Exclusion Criteria:
  1. A history of acute graft-versus-host disease grade III/IV or initiation of any new immunosuppressive agent within 4 weeks prior to enrollment.
  2. Use of prednisone at a dose of ≥0.25 mg/kg/day (or equivalent dose of another glucocorticoid) at the time of enrollment
  3. 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
  4. Presence of known HIV infection, active hepatitis B or C infection.
  5. Total bilirubin, aspartate transaminase, alanine transaminase 2 ´ the upper limit of the normal range. Patients with elevated bilirubin secondary to Gilbert syndrome will not be excluded.
  6. Creatinine clearance <30 mL/min
  7. 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 O2 saturation <90% by pulse oximetry
  8. Pregnancy or breastfeeding.
  9. Known hypersensitivity, or intolerance to any of the study medications, or excipients.
  10. Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
  11. 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.
  12. 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.

Relevance to patient case: not relevant