This phase I/II trial studies the side effects and best dose of ONC201 and to see how well it works alone and in combination with venetoclax in treating patients with acute leukemia or high-risk myelodysplastic syndrome that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). ONC201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ONC201 alone or in combination with venetoclax may be safe, tolerable, and/or effective in treating patients with relapsed or refractory acute leukemia or high-risk myelodysplastic syndrome.
Additional locations may be listed on ClinicalTrials.gov for NCT02392572.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Gautam Borthakur
Phone: 713-563-1586
PRIMARY OBJECTIVES:
I. To determine recommended phase II dose for oral dordaviprone (ONC201) alone or in combination with venetoclax in patients with relapsed or refractory acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) or acute lymphoblastic leukemia (ALL). (Phase I)
II. To identify toxicities associated with oral ONC201 alone or in combinationwith venetoclax in patients with relapsed or refractory AML, MDS or ALL. (Phase I)
III. To determine the objective response rate to ONC201 alone or in combination with venetoclax in patients with relapsed or refractory AML, MDS or ALL. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the pharmacokinetics (PK) of oral ONC201 alone or in combination with venetoclax. (Phase I)
II. To observe the anti-tumor effects of oral ONC201 alone or in combination with venetoclax in patients with relapsed or refractory AML, MDS or ALL. (Phase I)
III. Confirm tolerability of recommended phase II dose. (Phase II)
IV. Assess clinical outcomes associated with ONC201 alone or in combination with venetoclax treatment in patients with relapsed or refractory AML, MDS or ALL. (Phase II)
V. Correlate clinical outcome with tumor and serum biomarkers. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients are assigned to 1 of 6 arms.
ARM A: Patients receive ONC201 orally (PO) once every 3 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive ONC201 PO once every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive ONC201 PO on the first two consecutive days of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM D: Patients receive ONC201 PO once daily (QD). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM E: Patients receive ONC201 PO twice weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM F: Patients receive ONC201 PO twice weekly and venetoclax PO on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo chest x-ray at screening and blood sample collection, bone marrow aspiration and/or biopsy throughout the study.
After completion of study treatment, patients are followed up at 28 days.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorGautam Borthakur
