ONC201 in Relapsed/Refractory Acute Leukemias and High-Risk Myelodysplastic Syndromes (HR-MDS)

• Status: Active, not recruiting
• Trial end date: 2023-11-30
• Target enrollment: 0
• Participant gender: All

Summary

The goal of Phase I of this clinical research study is to find the highest tolerable dose of ONC201 alone or in combination with low dose cytarabine (LDAC) 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 given alone or in combination with LDAC that is 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.

ONC201 given alone or in combination with LDAC is in a very early stage of development for use in humans. Providing direct medical benefit to you is not the purpose of this study. While Phase II will look at the effectiveness of the study drug given alone or in combination with LDAC, the main purpose of this study is to learn about the safety of the drug.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Oncoceutics, Inc.
• Treatments: Cytarabine; TIC10 compound

Criteria

Inclusion Criteria:

1. For Arms A, B, C, D 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. For Arm E, in addition to patients with relapsed or refractory acute leukemias or high-risk MDS, patients with untreated high-risk MDS or acute leukemias will also be eligible provided they are not eligible for more intensive therapies.

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 bilirubin1.5 x the upper limit of normal (ULN) unless considered due to Gilbert's syndrome; (3) Alanine aminotransferase (ALT), or aspartate aminotransferase (AST)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.

Exclusion Criteria:

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 study requirements.

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.