A Phase Ib Study of the Safety, Feasibility, and Pharmacokinetics of AMG 386 Alone and in Combination With Low Dose Cytarabine in Acute Myeloid Leukemia (AML) Patients
I. To evaluate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD)
profile of AMG 386 (trebananib) when administered alone and in combination with low-dose
cytarabine in adult patients with: untreated AML considered ineligible for standard
induction chemotherapy; refractory and/or relapsed AML following at least one cycle of prior
therapy who are not currently eligible for stem cell transplantation.
I. To evaluate clinical responses in AML patients following AMG 386 therapy alone or in
combination with low-dose cytarabine therapy.
II. To characterize the biological changes occurring in AML patients treated with AMG 386
alone or in combination with low-dose cytarabine, specifically: alteration in Ang1, Ang2,
Tie2, vascular endothelial growth factor (VEGF), and VEGF receptor (VEGFR) expression;
changes in bone marrow vascularization and hypoxia; changes in gene and/or microRNA
expression; PK/PD modeling to characterize the time course of AMG 386 concentrations in
relation to target inhibition and hematological response.
III. To determine whether the above biological changes correlate with and/or predict for
clinical response in AML patients treated on this study.
OUTLINE: This is a dose-escalation study of trebananib. Patients are assigned to 1 of 2
ARM A: Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 5, 15,
ARM B: Patients receive trebananib as in Arm A. Patients also receive cytarabine
subcutaneously (SC) twice daily (BID) on days 1-14 of course 1 and days 1-7 of each
In both arms, treatment repeats every 28 days* for up to 12 courses in the absence of
disease progression or unacceptable toxicity.
NOTE: *Course 1 is 35 days.
After completion of study treatment, patients are followed up for 30 days and then
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability of trebananib when administered alone and in combination with low-dose cytarabine measured by number of participants with adverse events according to CTCAE
Adverse events will be tabulated overall and by arm.
Up to 30 days after the last dose of study drug
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of Rochester||Rochester, New York 14642|