BST-236, a novel cytarabine prodrug for patients with acute leukemia unfit for standard induction: a phase 1/2a study

High-dose cytarabine may be the backbone of acute myeloid leukemia (AML) treatment. Nonetheless, its use within older patients is significantly limited because of elevated toxicity. BST-236 (INN aspacytarabine) is really a novel cytarabine prodrug made to deliver high-dose cytarabine to focus on cells with reduced systemic contact with free cytarabine. This phase 1/2a dose-escalation study is built to evaluate BST-236 safety, pharmacokinetics, and effectiveness in older or unfit-for-intensive-therapy patients with acute leukemia. Twenty-six patients, unfit for normal therapy, who have been either relapsed/refractory or recently diagnosed, received BST-236 in 6 dose-escalating cohorts (range .three to six g/m2 each day). BST-236 was administered intravenously once daily over an hour for six consecutive days. The median age was 76.5 (26 to 90), with 84.6% of patients =70 years. BST-236 was safe and well tolerated. The maximal tolerated dose was 6 g/m2 each day. Overall response rate was 29.6%. A subgroup analysis of recently diagnosed patients with AML, de novo or secondary to myelodysplastic syndrome, unfit for normal induction (median age 78), shown overall response of 45.5%. The median overall survival was 6.5 several weeks and it was not arrived at in patients achieving complete remission. The findings of the phase 1/2 study claim that BST-236 securely delivers high and effective cytarabine doses to U-19920A older patients who’re unfit for normal induction and lays the building blocks for more studies of BST-236 in AML.