vorinostat + decitabine + fludarabine + cytarabine + filgrastim

This combination therapy regimen, investigated by the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium, is designed for pediatric and young adult patients with relapsed or refractory acute myeloid leukemia (AML). The regimen utilizes an epigenetic priming strategy, combining the histone deacetylase (HDAC) inhibitor vorinostat with the DNA methyltransferase inhibitor decitabine. This priming phase is intended to reprogram the leukemia cells' epigenome to restore normal gene expression and increase chemosensitivity. Following the priming, patients receive the FLAG chemotherapy backbone, which consists of fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF/filgrastim). A Phase 1 study (T2016-003/NCT02412475) established the safety and recommended Phase 2 dose for this multi-agent approach in children and young adults aged 1-25 years, demonstrating biological activity and promising response rates, particularly in patients with known epigenetic alterations.

Other names

Decitabine and Vorinostat followed by FLAGVorinostat + Decitabine + FLAGTACL T2016-003 regimen