Clinical Trials /

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

NCT03932643

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: ONC 201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After Stem Cell Transplant
  • Official Title: A Pilot Study of ONC 201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After an Allogeneic Hematopoietic Stem Cell Transplant

Clinical Trial IDs

  • ORG STUDY ID: 274-19
  • NCT ID: NCT03932643

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
ONC201ONC201 treatment

Purpose

This is a single-center pilot study 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.

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 6-20 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.
    

Trial Arms

NameTypeDescriptionInterventions
ONC201 treatmentExperimentalA 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.
  • ONC201

Eligibility Criteria

        Inclusion Criteria:

          1. A history of AML or 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 used indefined 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.

          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. Karnofsky Performance Status (KPS) of ≥70

          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 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.

          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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The rate of dose limiting toxicities during the first cycle (among the dose escalating cohort)
Time Frame:after one month of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of toxicities (all grades) associated with the use of ONC 201 during the entire duration of maintenance therapy with ONC 201
Time Frame:upto 13 months after initiation of ONC 201
Safety Issue:
Description:
Measure:The rate of relapse
Time Frame:upto 2 years after enrollment
Safety Issue:
Description:
Measure:The rate of relapse-free survival
Time Frame:upto 2 years after enrollment
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vijaya Bhatt

Last Updated

March 14, 2020