Perlmutter Cancer Center

The optimal treatment for children and adolescents with Ph+ ALL has not yet been determined. There is now a general consensus among the North American and European Childhood ALL treatment groups that Ph+ ALL patients with a favorable early response to the combination of chemotherapy and tyrosine kinase inhibitor (TKI) treatment can be treated without HSCT in first complete remission (CR1), while those with a suboptimal early response are more appropriately treated with HSCT in CR1. Two different cytotoxic chemotherapy backbones have been used in combination with TKI in recent North American and European pediatric Ph+ ALL trials: 1) the COG regimen (used in COG AALL0031with imatinib and in AALL0622 with dasatinib), and 2) the EsPhALL regimen used in Europe with imatinib (initial EsPhALL trial) and in a joint COG/EsPhALL (AALL1122) trial with dasatinib. Both of these regimens are quite intensive, leading to a high frequency of treatment-related complications, including prolonged myelosuppression and life-threatening infections. On AALL1122, approximately 5% of patients treated with the EsPhALL regimen plus TKI without HSCT died due to toxicity, accounting for a significant percentage of events observed in the non-HSCT population in these trials. The goal of this trial is to reduce treatment-related morbidity and mortality without adversely impacting disease free survival (DFS) in Standard Risk (SR) patients, who comprise approximately 80-85% of all pediatric Ph+ ALL patients. The proposed AALL1631 trial will test whether favorable outcomes may be achieved when imatinib is combined with a less intensive chemotherapy backbone in pediatric Ph+ ALL patients defined as SR based on MRD measurements early in treatment. We plan to randomly compare the two cytotoxic backbones using a non-inferiority design in order to detect whether there is a lack of significant decrement in DFS with the less intensive chemotherapy regimen. The randomized trial design will also allow us to directly compare toxicities associated with the two regimens.