ONC-201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant

NCT03932643 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 0274-19-FB
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center Phase 1 trial of 20 patients with AML/MDS. Eligible patients will be enrolled following an informed consent between 6-20 weeks after allogeneic hematopoietic stem cell transplant. Patients will receive weekly oral ONC 201 for a total of 52 weeks.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (2)

• Rate of dose limiting toxicities during the first cycle

  The rate of dose limiting toxicities during the first cycle (among the dose escalating cohort)

  after one month of treatment

• Grade ≥3 toxicities

  The number of grade ≥3 toxicities

  during the first 3 cycles ot treatment (each cycle is 28 days)

Secondary Outcomes (3)

• Number of toxicities (all grades) during the duration of maintenance therapy with ONC 201

  upto 13 months after initiation of ONC 201

• The rate of relapse

  upto 2 years after enrollment

• The rate of relapse-free survival

  upto 2 years after enrollment

Study Arms (1)

ONC-201 Treatment

EXPERIMENTAL

A 3+3 dose escalation design will be followed. Given the safety profile in prior trials, A dose of 250 mg weekly will be the starting dose. The first 12-15 patients are expected to receive escalating doses of ONC 201, the remaining patients will go on the expansion cohort.

Drug: ONC-201

Interventions

ONC-201 DRUG

ONC-201 Capsules, 125 mg Oral ONC-201 at various dose levels will be given at weekly intervals for up to 13 cycles (52 weeks); 4-week therapy will be considered 1 cycle.

Also known as: dordaviprone

ONC-201 Treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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), 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 defined by the Revised International Prognostic Scoring System (e.g. complex karyotype with ≥3 changes),53 the presence of TP53 mutation, 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/µL without the use of granulocyte colony stimulating factor in the past 2 weeks, and platelet count 50,000/µL 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.
• 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
• Written informed consent to participate in the study.

You may not qualify if:

• 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 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 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)
• 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.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

TIC10 compound

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Vijaya R Bhatt, MBBS

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2019
• First Posted: May 1, 2019
• Study Start: July 30, 2019
• Primary Completion: March 27, 2025
• Study Completion: March 27, 2025
• Last Updated: January 20, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)