A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)
A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)
The purpose of this study is to evaluate the safety and tolerability of AGS67E in subjects with acute myeloid leukemia (AML) and determine a safe dose for future development. In addition, this study will assess the pharmacokinetics (PK), the immunogenicity, and the anti-leukemic activity of AGS67E.
The study will sequentially evaluate AGS67E given as a 30 minute intravenous (IV) infusion in two different schedules: once every 3 weeks (Q3) and then once weekly for 3 weeks.
The dose escalation follows a 3 + 3 design.
The Data Review Team may expand any dose level or intermediate dose level that has been deemed safe and resulted in at least one subject with a Composite Complete Remission (CRc). An expansion cohort may enroll up to 15 subjects.
Inclusion Criteria:
Subject has morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2008) and fulfills one of the following:
Circulating blasts < 20,000 (cytoreduction with hydroxyurea is allowed)
Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2
Subject has adequate renal function: serum creatinine ≤ 2.0 mg/dL and estimated creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation
Subject has a total bilirubin ≤ 1.5 x upper limit of normal (ULN), albumin ≥ 2.5 g/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
Negative pregnancy test in women of child bearing potential
Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 weeks after termination of study therapy
Exclusion Criteria:
Subject has a diagnosis of acute promyelocytic leukemia
Subject has preexisting sensory or motor neuropathy Grade ≥ 2 at baseline
Subject has received small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, investigational drug, or chemotherapy within 14 days before first dose of study drug, with the exception of hydroxyurea
P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days before the first dose of drug, with the exception of the antibiotics/ antifungals used as prophylaxis and/or supportive care
Any Grade ≥ 2 persistent non-hematological toxicity related to allotransplant
Graft-Versus-Host Disease (GVHD) therapy within 6 weeks before the first dose of study drug; low dose steroids (≤ 10mg) allowed
Subject has known current central nervous system (CNS) disease
Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
Subject has clinical evidence of Disseminated Intravascular Coagulation (DIC)
Subject has known positivity for human immunodeficiency virus (HIV)
Subject has know positivity for Hepatitis B surface antigen test or Hepatitis C Antibody
Subject has an uncontrolled active infection requiring treatment and fever 38.3°C or higher 48 hours before the first dose of study drug. Controlled infections (i.e. 3 negative cultures completing antibiotics and/or stable fungal infection in therapy are allowed provided the subject has a temperature of <38.3°C within 48 hours of the first dose of study drug
Subject has known sensitivity to any of the components of the investigational product AGS67E:
Major surgery within 28 days of the first dose of study drug
Subject is pregnant or lactating
Subject has a condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study