Phase I/II Study of Oral ONC201 in Patients with Relapsed or Refractory Acute Leukemias and High-risk Myelodysplastic Syndromes
The goal of Phase I of this clinical research study is to find the highest tolerable dose of ONC201 that can be given to patients with relapsed or refractory AML, ALL, or MDS. The goal of Phase II of this study is to learn if the dose of ONC201 found in Phase I can help to control the disease. The safety of the study drug will be studied in both phases of this study. This is the first study using ONC201 in humans.
Disease Group: Leukemia
Treatment Agent: ONC201
Treatment Location: Only at MD Anderson
Sponsor: Oncoceutics, Inc.
Primary Objectives of Phase I To determine recommended phase II dose for oral ONC201 in patients with relapsed or refractory acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) or acute lymphoblastic leukemia (ALL). To identify toxicities associated with oral ONC201 in patients with relapsed or refractory AML, MDS or ALL. Secondary Objectives of Phase I To determine the pharmacokinetics (PK) of oral ONC201 following administration. To observe the anti-tumor effects of oral ONC201, if any occur, in patients with relapsed or refractory AML, MDS or ALL. Primary Objectives of Phase II To determine the objective response rate to ONC201 in patients with relapsed or refractory AML, MDS or ALL. Secondary Objectives of Phase II Confirm tolerability of recommended phase II dose. Assess clinical outcomes associated with ONC201 treatment in patients with relapsed or refractory AML, MDS or ALL. Correlate clinical outcome with tumor and serum biomarkers.
IRB Review and Approval Date: 11/03/2015
Recruitment Status: Open
Projected Accrual: N/A
1) Patients must have relapsed or refractory acute leukemias or
high-risk MDS for which no standard therapies are anticipated to result
in a durable remission.
2) Age >/=18 years.
3) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4) Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device, such as a condom, diaphragm, or cervical/vault cap), for 16 weeks after the last dose of study drug, and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods for the duration of time on study and for at least 16 weeks after the last dose of study drug. Pregnant and nursing patients are excluded because the effects of ONC201on a fetus or nursing child are unknown.
5) Must be able and willing to give written informed consent.
6) The interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. If the patient is on hydroxyurea to control peripheral blood leukemic cell counts, the patient must be off hydroxyurea for at least 24 hours before initiation of treatment on this protocol. Persistent clinically significant toxicities from prior therapy must not be greater than grade 1.
7) Patients must have the following clinical laboratory values unless considered due to leukemic organ involvement: (1) Serum creatinine < 2.0 mg/dl; (2) Total bilirubin </= 1.5 x the upper limit of normal (ULN) unless considered due to Gilbert’s syndrome; (3) Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) </= 3 x the ULN unless considered due to organ leukemic involvement.
8) Patients with known central nervous system (CNS) disease are allowed if there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least 2 weeks prior to study drug administration. Information obtained from standard of care historical data will be used for this purpose.
9) Relapse > 6 months since autologous or allogeneic stem cell transplantation provided: (1) No active graft-versus-host disease (GVHD > grade 1); (2) No treatment with high dose steroids for GVHD (up to >/= 20 mg Prednisolone or equivalent per day); (3) No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus.
1) Uncontrolled intercurrent illness including, but not limited to
uncontrolled infection, symptomatic congestive heart failure (New York
Heart Association class III and IV), uncontrolled cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with
2) Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure (New York Heart Association class III and IV).
3) Patients receiving any other standard or investigational treatment for their hematologic malignancy within past 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents.
4) Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy.
5) Known history of seropositive for human immunodeficiency virus (HIV) antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or a Hepatitis B carrier (positive for Hepatitis B surface antigen [HBsAg])
6) Active drug use or alcoholism.
Information and next steps
Phase I/Phase II
For general questions about clinical trials: