A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)

Astellas

Status and phase: Terminated; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: AGS67E

Study type: Interventional

Funder types: Industry

Identifiers

NCT02610062

AGS67E-15-2

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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23 participants in 5 patient groups

AGS67E 1.2 mg/kg Schedule 1

Experimental group

Description:

Participants will receive 1.2 mg/kg of AGS67E as an intravenous infusion once every three weeks (Q3).

Treatment:

Drug: AGS67E

AGS67E 1.8 mg/kg Schedule 1

Experimental group

Description:

Participants will receive 1.8 mg/kg of AGS67E as an intravenous infusion once every three weeks.

Treatment:

Drug: AGS67E

AGS67E 2.4 mg/kg Schedule 1

Experimental group

Description:

Participants will receive 2.4 mg/kg of AGS67E as an intravenous infusion once every three weeks.

Treatment:

Drug: AGS67E

AGS67E 0.6 mg/kg Schedule 2

Experimental group

Description:

Participants will receive 0.6 mg/kg of AGS67E once weekly for three weeks.

Treatment:

Drug: AGS67E

AGS67E 0.9 mg/kg Schedule 2

Experimental group

Description:

Participants will receive 0.9 mg/kg of AGS67E once weekly for three weeks.

Treatment:

Drug: AGS67E