Unexpectedly, we identified the anthelmintic agents moxidectin, ivermectin, and milbemycin to have a high anti-leukemic potential as single agents and to exhibit synergistic activity with the BCL-2 inhibitor navitoclax (ABT-263) and standard chemotherapeutic agents of frontline ALL therapy, such as dexamethasone in highly refractory primary ALL. The gene discussed is BCL2; the disease is acute lymphoblastic leukemia.