Efficacy and Safety Study of Recombinant Human Arginase 1 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

This is a phase 2, non-randomised, open-label study that aims at evaluating the efficacy of single agent PEG-BCT-100 in adult patients with relapsed/refractory AML. Eligible patients will receive intravenous (IV) infusion of PEG-BCT-100 weekly until disease progression, unacceptable drug-related toxicity(ies), allogeneic haematopoietic stem cell transplantation or withdrawal of subject consent. Pharmacokinetic (PK) of PEG-BCT-100 and pharmacodynamics (PD) activity of PEG-BCT-100 on arginine depletion will be evaluated throughout the study. Plasma arginine level, intracellular blast arginine level (IBAL) in peripheral blood (PB) and bone marrow (BM) will be measured at specific time points. PEG-BCT-100 will be given once weekly at 1600 Units/kg (2.7mg/kg) per dose for three weeks (Cycle 1). If the post-treatment IBAL-BM examined within 5 days prior to each cycle fails to drop at least 70% from baseline value and disease response fails to achieve complete remission (CR) or complete remission with incomplete blood count recovery (CRi), PEG-BCT-100 may be increased to 2500 U/kg (the maximum tolerated dose as reported previously) at investigator's discretion. Disease response will be assessed within 5 days prior to each cycle according to the International Working Group (IWG) AML Response Criteria. Safety and toxicity will be assessed through physical examinations, vital signs, blood tests and urinalysis throughout the study. Adverse event (AE) and serious adverse events (SAE) will be reported according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.03 (CTCAE v4.03) until 28 days after the last dose of PEG-BCT-100. Immunogenicity response including anti-drug antibody (ADA) level and neutralizing antibody level will be assessed weekly for the first 2 cycles of PEG-BCT-100, pre-dose of each cycle thereafter and End of Study (EoS). Specific response predictive biomarkers in circulating and BM blasts, and emerging genetic markers will also be explored in the study.