A Phase I/II of Nivolumab in Combination with Chemotherapy in pediatric patients with relapsed/refractory acute myeloid leukemia

Pediatric Blood Cancer
Anupam Verma, MD
University of Utah


Despite advances in treatment of AML, the long-term survival rate of children with relapsed AML has not changed significantly and remains poor. Intensification of conventional chemotherapy leads to increases in drug toxicity without improvement in outcomes. Therefore, novel therapeutic strategies are warranted. This phase I/II study will evaluate the feasibility and safety of nivolumab, an immunotherapy, in combination with 5-azacytidine, a chemotherapeutic, in children with relapsed or refractory AML. Cancer cells evolve and develop protective mechanisms to hide themselves from cancer killing T-cells. Nivolumab blocks these protective mechanisms, unhiding cancer cells so that they can be killed by T-cells. However, cancer cells have other methods of being resistant, including aberrant DNA methylation. Aberrant DNA methylation is associated with relapse and the development of drug resistance in AML. For this reason, the investigators suggest combining nivolumab with 5-azacytidine, a DNA demethylation (removing methylation) agent, will reverse aberrant DNA methylation combating multiple resistance mechanisms.

Trial Registration: ClinicalTrials.gov Identifier: NCT03825367