Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia

PRIMARY OBJECTIVE: I. To determine the safety, tolerability, and recommended phase II dose (RP2D) of uproleselan combined with cladribine + low dose cytarabine (LDAC) in patients with treated-secondary acute myeloid leukemia (AML) (ts-AML). SECONDARY OBJECTIVES: I. To assess the efficacy (overall response rate \[ORR\], complete response \[CR\], complete response without blood count recovery \[CRi\], CR with partial hematologic recovery \[CRh\], partial response \[PR\], or morphologic leukemia-free state of uproleselan combined with cladribine + LDAC in patients with ts-AML. II. To assess the rate of minimal residual disease (MRD) negativity by flow cytometry at response. III. To assess overall survival (OS), remission duration (CRd), and progression-free survival (PFS) in patients with ts-AML treated with uproleselan combined with cladribine + LDAC. IV. To assess the rate of complete cytogenetic response (CCyR) in patients with ts-AML with abnormal baseline karyotype, treated with uproleselan combined with cladribine + LDAC. V. To assess toxicity and induction mortality of patients with AML treated with uproleselan added to cladribine + LDAC. EXPLORATORY OBJECTIVES: I. To explore biomarkers of response and resistance in patients with ts-AML treated with uproleselan combined with cladribine + LDAC. II. To examine the correlation of E-selectin ligand-forming glycosylation genes of leukemic blasts with clinical outcome. OUTLINE: This is a phase I, dose-escalation study of cladribine and cytarabine followed by a phase II study. INDUCTION THERAPY: Patients receive uproleselan intravenously (IV) over 20 minutes on day 1 and every (Q) 12 hours on days 2-12, cladribine IV over 1-2 hours on days 1-5 and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle. CONSOLIDATION/MAINTENANCE THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q12 hours on days 2-1. Patients who have achieved at least CR/CRi or morphologic leukemia-free state after induction therapy receive uproleselan IV once daily (QD) on days 1-12. Patients also receive cladribine IV over 1-2 hours on days 1-3 and cytarabine SC BID on days 1-10. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 months.