Fludarabine, Cytarabine, and Pegcrisantaspase for the Treament of Relapsed or Refractory Leukemia

PRIMARY OBJECTIVE: I. To determine the safety and tolerability of fludarabine, cytarabine (araC), and pegcrisantaspase in patients with relapsed and refractory leukemias. SECONDARY OBJECTIVES: I. To determine the overall response rate (complete remission \[CR\], CR with incomplete count recovery \[CRi\], partial remission \[PR\], or morphologic leukemia free state \[MLFS\]) of a lead-in dose of single-agent pegcrisantaspase in patients with relapsed and refractory leukemias. II. To determine the overall response rate (complete remission \[CR\], CR with incomplete count recovery \[CRi\], partial remission \[PR\], or morphologic leukemia free state \[MLFS\]) of fludarabine, araC, and pegcrisantaspase in patients with relapsed and refractory leukemias. III. To assess overall survival (OS) and disease-free survival (DFS) of patients treated with fludarabine, araC, and pegcrisantaspase. IV. To assess the duration of response to the combination in patients with advanced leukemias. V. To characterize the pharmacokinetics (PK) pharmacodynamics (PD) anti-drug antibodies (ADA) of pegcrisantaspase in patients with relapsed and refractory leukemias. EXPLORATORY OBJECTIVE: I. Explore pretreatment and on-treatment biological correlates to predict sensitivity/resistance of pegcrisantaspase-based therapy. OUTLINE: This is a dose-escalation study of pegcrisantaspase. INDUCTION: Patients receive pegcrisantaspase intravenously (IV) over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-11 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-10. Treatment repeats every 5 weeks for up 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 months.