COG has initiated three protocols that introduce novel agents into treatment regimens for children with newly diagnosed ALL:
The ALL0434 protocol is evaluating whether the addition of nelarabine to a standard ALL regimen can improve outcome for children with T-cell ALL. COG previously demonstrated that nelarabine can induce complete remissions as a single agent in children with recurrent T-cell ALL.
The ALL0622 protocol is studying whether the Src/Abl inhibitor dasatinib can improve outcome for children with Philadelphia chromosome positive (Ph+) ALL when it is administered concurrently with standard agents used to treat ALL. Dasatinib is approved for the treatment of imatinib-refractory chronic myeloid leukemia (CML), and it has shown single-agent activity in children and adults with Ph+ ALL.
The ALL0631 study is evaluating the FLT3 inhibitor lestaurtinib (CEP-701) in infants with ALL whose leukemia cells have translocations involving the myeloid/lymphoid or mixed-lineage leukemia (MLL) gene. The FLT3 kinase is consistently highly expressed and activated in ALL with the MLL gene rearrangement. FLT3 inhibitors selectively kill ALL cells with the MLL gene rearrangement in vitro and in vivo, and they synergize with chemotherapy.
COG is also studying molecularly targeted agents in children with relapsed ALL and has protocols evaluating the mTOR inhibitor rapamycin and the CD22-targeted monoclonal antibody epratuzumab.