The Children’s Oncology Group (COG) has initiated three protocols that introduce novel agents into treatment regimens for children with newly diagnosed acute lymphoblastic leukemia (ALL):
The AALL0434 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. (http://www.cancer.gov/clinicaltrials/COG-AALL0434)
The AALL0622 protocol is studying whether 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. (http://www.cancer.gov/clinicaltrials/COG-AALL0622)
The AALL0631 study is evaluating a tyrosine kinase inhibitor lestaurtinib (CEP-701) in infants with ALL whose leukemia cells have translocations involving the myeloid/lymphoid or mixed-lineage leukemia (MLL) gene. This particular tyrosine 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. (http://www.cancer.gov/clinicaltrials/COG-AALL0631)
COG is also studying molecularly targeted agents in children with relapsed ALL and has protocols evaluating the mTOR inhibitor rapamycin (http://www.cancer.gov/clinicaltrials/COG-ASCT0431) and the targeted monoclonal antibody epratuzumab (http://cancer.gov/clinicaltrials/COG-ADVL04P2).