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Blood Adv. 2019 Nov 26;3(22):3740-3749. doi: 10.1182/bloodadvances.2019000468.

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

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Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Hematology Division, Sourasky Medical Center, Tel-Aviv, Israel.
Department of Hematology, Galil Medical Center, Nahariya, Israel.
Department of Hematology, Assaf Harofeh Medical Center, Zerifin, Israel.
Department of Hematology, Assuta Medical Center, Tel Aviv, Israel.
Department of Hematology, Poria Medical Center, Tiberias, Israel.
BioSight Ltd, Airport City, Lod, Israel; and.
Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.


High-dose cytarabine is the backbone of acute myeloid leukemia (AML) treatment. Nevertheless, its use in older patients is considerably limited due to increased toxicity. BST-236 (INN aspacytarabine) is a novel cytarabine prodrug designed to deliver high-dose cytarabine to target cells with reduced systemic exposure to free cytarabine. This phase 1/2a dose-escalation study was designed to evaluate BST-236 safety, pharmacokinetics, and efficacy in older or unfit-for-intensive-therapy patients with acute leukemia. Twenty-six patients, unfit for standard therapy, who were either relapsed/refractory or newly diagnosed, received BST-236 in 6 dose-escalating cohorts (range 0.3 to 6 g/m2 per day). BST-236 was administered intravenously once daily over 60 minutes for 6 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 per day. Overall response rate was 29.6%. A subgroup analysis of newly diagnosed patients with AML, de novo or secondary to myelodysplastic syndrome, unfit for standard induction (median age 78), demonstrated overall response of 45.5%. The median overall survival was 6.5 months and was not reached in patients achieving complete remission. The findings of this phase 1/2 study suggest that BST-236 safely delivers high and efficacious cytarabine doses to older patients who are unfit for standard induction and lays the foundation for further studies of BST-236 in AML. This trial was registered at as #NCT02544438.

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