NCT01861314

Bortezomib, Sorafenib Tosylate, and Decitabine in Treating Patients With Acute Myeloid Leukemia

Phase I Study of The Combination of Bortezomib and Sorafenib Followed by Decitabine in Patients With Acute Myeloid Leukemia

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of bortezomib and sorafenib tosylate when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, 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 bortezomib and sorafenib tosylate together with decitabine may work better in treating acute myeloid leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To identify the biologically effective and tolerable dose (BETD) of the bortezomib/sorafenib (sorafenib tosylate) combination in acute myeloid leukemia (AML) with biological activity defined as the dose(s) that induce a 100% increase (i.e. a doubling) in the level of microRNA-29b (miR-29b) in bone marrow (BM) after bortezomib/sorafenib treatment from pretreatment levels in at least 5 out of 6 patients at a given dose levels. II. To recommend a dose level for a Phase II study using this agent combination in patients with AML. III. To define the specific toxicities and the dose limiting toxicity (DLT) of bortezomib in combination with sorafenib and decitabine. SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) of this combination. II. To determine the rate of complete remission (CR) of this combination. III. To conduct pharmacodynamic studies by measuring the effect of this chemotherapy combination on the micronome, kinome and epigenome. OUTLINE: This is a dose-escalation study of bortezomib and sorafenib tosylate. STEP A: Patients receive bortezomib subcutaneously (SC) on days 1 and 4, sorafenib tosylate orally (PO) twice daily (BID) on days 1-14, and decitabine intravenously (IV) over 1 hour on days 5-14. STEP B: Patients receive bortezomib SC on days 1, 4, and 8 or 1, 4, 8 and 11, sorafenib tosylate PO BID on days 1-14, and decitabine IV over 1 hour on days 9-18 or 12-21. STEP C: Patients receive bortezomib SC on days 1, 4, and 8 or 1, 4, 8 and 11, sorafenib tosylate PO BID on days 1-14, and decitabine IV over 1 hour on days 5-14. Treatment repeats every 28 days for up to 4 courses in the absence of unacceptable toxicity. Patients achieving complete response (CR) or incomplete CR (CRi) receive maintenance therapy comprising decitabine IV on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.

Conditions

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia Post Cytotoxic Therapy
• Recurrent Adult Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Bortezomib	Given SC
DRUG	Decitabine	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Sorafenib Tosylate	Given PO

Timeline

• Start date: 2013-07-03
• Primary completion: 2015-11-06
• Completion: 2027-03-19
• First posted: 2013-05-23
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study