NCT02392572

ONC201 in Treating Patients With Relapsed or Refractory Acute Leukemia or High-Risk Myelodysplastic Syndrome

Phase I/II Study of Oral ONC201 in Patients With Relapsed or Refractory Acute Leukemias and High-Risk Myelodysplastic Syndromes

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of ONC201 and to see how well it works in treating patients with acute leukemia or high-risk myelodysplastic syndrome that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). ONC201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: To determine recommended phase II dose for oral ONC201 (\[Akt/ERK inhibitor 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 combination with VENETOCLAX in patients with relapsed or refractory AML, MDS or ALL. (Phase I) III. To determine the objective response rate to ONC201 alone 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 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 5 arms. ARM A: Patients receive Akt/ERK inhibitor 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 Akt/ERK inhibitor ONC201 PO once every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive Akt/ERK inhibitor 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 Akt/ERK inhibitor ONC201 PO once daily (QD). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM E: Patients receive Akt/ERK inhibitor ONC201 PO twice weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM F: Patients receive Akt/ERK inhibitor ONC201 PO twice weekly for 4 weeks and venetoclax daily on days 1-21 every 28 day cycle. After completion of study treatment, patients are followed up at 28 days.

Conditions

• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia
• Refractory Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Akt/ERK Inhibitor ONC201	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2015-11-03
• Primary completion: 2026-11-30
• Completion: 2026-11-30
• First posted: 2015-03-19
• Last updated: 2026-04-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study