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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.

Author information

1
Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
2
The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
3
Hematology Division, Sourasky Medical Center, Tel-Aviv, Israel.
4
Department of Hematology, Galil Medical Center, Nahariya, Israel.
5
Department of Hematology, Assaf Harofeh Medical Center, Zerifin, Israel.
6
Department of Hematology, Assuta Medical Center, Tel Aviv, Israel.
7
Department of Hematology, Poria Medical Center, Tiberias, Israel.
8
BioSight Ltd, Airport City, Lod, Israel; and.
9
Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.

Abstract

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 www.clinicaltrials.gov as #NCT02544438.

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