a study to evaluate safety, tolerability, and pharmacokinetics of escalating doses of ags67e given as monotherapy in subjects with acute myeloid leukemia (aml)

Conditions: Acute Myeloid Leukemia

Summary: 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.

Eligibility criteria:
inclusion criteria: * subject has morphologically documented primary or secondary aml by the world health organization (who) criteria (2008) and fulfills one of the following: * refractory to at least 1 cycle of induction chemotherapy * relapsed after achieving remission with a prior therapy * patients with untreated aml who are either unwilling or unable to undergo high-dose induction/consolidation intensive chemotherapy * 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: * ags67e * l-histidine * α-trehalose dihydrate or * polysorbate 20 * 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

Keywords: aml acute myeloid leukemia