inecalcitol + decitabine

Inecalcitol + decitabine is an investigational **combination therapy** being evaluated for the treatment of acute myeloid leukemia (AML), specifically in patients unfit for standard induction chemotherapy. **Inecalcitol** is a synthetic vitamin D receptor agonist that enhances the expression of vitamin D-responsive genes, potentially limiting leukemia progression by promoting cell differentiation and inhibiting proliferation through activation of the vitamin D receptor. **Decitabine** is a DNA hypomethylating agent that incorporates into cellular DNA and inhibits DNA (cytosine-5)-methyltransferases, leading to hypomethylation, reactivation of silenced tumor suppressor genes, and cytotoxicity at higher doses. The rationale for the combination is mechanistic: decitabine helps "unmask" the vitamin D receptor gene by reducing methylation in its promoter, enhancing inecalcitol’s activity and resulting in a synergistic anti-leukemic effect. The combination's development was primarily pursued by Hybrigenics, which received Orphan Drug Designation for inecalcitol in AML and led a Phase II clinical trial combining inecalcitol and decitabine in older or frail AML patients. However, the Phase II trial was terminated prematurely[1][3][4].