Front-line Treatment of Ph Positive (Ph+)/Bcr-Abl Positive Acute Lymphoblastic Leukemia (ALL) With Two Tyrosine Kinase Inhibitors (TKI) (Imatinib and Nilotinib). A Phase II Exploratory Multicentric Study in Elderly Patients and in Patients Unfit for Program of Intensive Therapy and Allogeneic Stem Cell Transplantation. GIMEMA Protocol LAL1408. EudraCT 2009-01327122

This study is an open-label, multicentric, exploratory, single arm, phase II study of adults who are either more than 60 years old, or are unfit for intensive chemotherapy and allo SCT. The patients are treated with NILOTINIB, administered orally twice daily, for 6 weeks (Course A) followed by IMATINIB, administered orally twice daily, for other 6 weeks (Course B).The courses will be repeated (rotated) for a total of 4 times or until relapse, or until it is in the interest of the patients. Prednisone (P) will be administered to all patients for 7-14 days, before TKIs, so as to make it possible to wait for the results of cytogenetic and molecular tests, and to evaluate the response to P alone, hence for another 21 days. Intrathecal therapy (IT) with MTX/AraC/DEX is mandatory, monthly, in patients without clinical-cytologic evidence of meningeal involvement, while in patients with CNS involvement it is performed twice weekly until clearance of leukemic cells, hence once weekly. IM will be administered at the dosage of 600 mg daily (300 mg twice daily) and Nilotinib at the dosage of 800 mg daily (400 mg twice daily) in all courses.

All patients are scheduled to receive at least 4 courses of either drugs, for a total of 4 courses (4 x 6 = 24 weeks). After 4 courses, patients are either allowed to continue the treatment until relapse or progression, if it is in their interest, or to discontinue the treatment and receive other therapies.