AALL1231 - A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239; IND# 58443) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T- Lymphoblastic Leukemia (T-ALL)and T- Lymphoblastic Lymphoma (T-LLy)A Groupwide Phase III Study
Primary Aims: To compare EFS in patients with newly diagnosed T-ALL and T-LLy who are randomized to a modified ABFM backbone versus bortezomib plus the modified ABFM backbone.
1)To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based Induction, additional doses of pegaspargase (PEG-ASP) during Induction and Delayed Intensification (DI), and dexamethasone pulses during Maintenance therapy
2)To determine if prophylactic (presymptomatic) cranial radiation therapy (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified as
standard or intermediate risk.
3)To determine the proportion of EOC MRD ¿ 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible for other treatment strategies, including hematopoietic stem cell transplant (HSCT).
Similarly, to compare the EFS between very high risk (Induction failure) T-LLy
patients treated with HR BFM intensification blocks who have partial or complete response (PR or CR) with those who do not respond (NR).
1)To investigate the prognostic significance of Day 29 BM MRD in T-LLy patients.
2)To determine if protein expression patterns can predict bortezomib response and drug resistance in T-ALL
3)To analyze and target relevant signaling pathways in T-ALL blasts, focusing on Early T cell Precursor (ETP) ALL