Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03932643
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : March 17, 2020
Sponsor:
Information provided by (Responsible Party):
Vijaya Bhatt, University of Nebraska

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

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Drug: ONC201 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of ONC 201 Maintenance Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndrome After an Allogeneic Hematopoietic Stem Cell Transplant
Actual Study Start Date : July 30, 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2024


Arm Intervention/treatment
Experimental: ONC201 treatment
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: ONC201

ONC201 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.





Primary Outcome Measures :
  1. The rate of dose limiting toxicities during the first cycle (among the dose escalating cohort) [ Time Frame: after one month of treatment ]
  2. The number of grade ≥3 toxicities [ Time Frame: during the first 3 cycles ot treatment (each cycle is 28 days) ]

Secondary Outcome Measures :
  1. 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 ]
  2. The rate of relapse [ Time Frame: upto 2 years after enrollment ]
  3. The rate of relapse-free survival [ Time Frame: upto 2 years after enrollment ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03932643


Contacts
Layout table for location contacts
Contact: Penny nurse coordinator 4025594135 penny.hardiman@unmc.edu
Contact: Peggy Heires peggy.heires@unmc.edu

Locations
Layout table for location information
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
Vijaya Bhatt
Investigators
Layout table for investigator information
Principal Investigator: Vijaya R Bhatt, MBBS University of Nebraska
Layout table for additonal information
Responsible Party: Vijaya Bhatt, Associate Professor, University of Nebraska
ClinicalTrials.gov Identifier: NCT03932643    
Other Study ID Numbers: 274-19
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: March 17, 2020
Last Verified: March 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions