Phase I Study of the Combination of Bortezomib and Sorafenib Followed by Decitabine in Elderly Patients With Acute Myeloid Leukemia
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 older
patients with AML.
III. To define the specific toxicities and the dose limiting toxicity (DLT) of bortezomib in
combination with sorafenib and decitabine.
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
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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
BETD of bortezomib, sorafenib tosylate, and decitabine using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4
Analysis will include summarization of the toxicity and tolerability by dose level. Frequency and severity of adverse events and tolerability of the regimen in each of the dose levels will be collected and summarized using descriptive statistics.
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|