NCT03063944

STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory, Relapsed or Newly Diagnosed and Ineligible for Intensive Chemotherapy

Phase I Trial of OPB-111077 in Combination With Decitabine and Venetoclax for the Treatment of AML Refractory to or Ineligible for Intensive Chemotherapy

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of STAT inhibitor OPB-111077 when given together with decitabine and venetoclax in treating patients with acute myeloid leukemia that does not respond to treatment (refractory), has come back (relapsed), or is newly diagnosed and ineligible for intensive chemotherapy. STAT inhibitor OPB-111077 and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving STAT inhibitor OPB-111077, decitabine, and venetoclax may work better in treating patients with acute myeloid leukemia compared to decitabine alone.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety and tolerability of STAT inhibitor OPB-111077 (OPB-111077) in combination with decitabine and venetoclax. SECONDARY OBJECTIVES: I. To describe any preliminary efficacy of OPB-111077 in combination with decitabine and venetoclax in patients with acute myeloid leukemia (AML). II. To measure adenosine triphosphate (ATP) generation and perform metabolomics in patients with AML who are receiving OPB-111077, decitabine, and venetoclax. III. To assess apoptosis and proliferation assays in patients with AML who are receiving OPB-111077, decitabine, and venetoclax. OUTLINE: This is a dose escalation study of STAT inhibitor OPB-111077. INDUCTION CYCLE 1: Patients receive STAT inhibitor OPB-111077 orally (PO) once daily (QD) on days 1-28, and venetoclax PO QD on days 4-28 of cycle 1. Patients also receive decitabine intravenously (IV) over approximately 1 hour on days 4-8 of cycle 1. Patients who achieve complete remission (CR) after 1 cycle move on to Maintenance, and patients who do not achieve a CR move on to Cycle 2. INDUCTION CYCLE 2: Patients receive STAT inhibitor OPB-111077, venetoclax, and decitabine as in Induction Cycle 1. Patients who achieve CR, complete remission with incomplete hematologic recovery (CRi), partial remission (PR), or stable disease (or clinically significant hematologic improvement as determined by the investigator) move on to Maintenance. MAINTENANCE: Patients receive STAT inhibitor OPB-111077, venetoclax, and decitabine as in Induction Cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.

Conditions

• Acute Myeloid Leukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	STAT Inhibitor OPB-111077	Given PO
DRUG	Decitabine	Given IV
DRUG	Venetoclax	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies

Timeline

• Start date: 2017-03-17
• Primary completion: 2024-01-18
• Completion: 2024-03-04
• First posted: 2017-02-24
• Last updated: 2025-05-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study