Nilotinib, a new BCR-ABL tyrosine kinase inhibitor, was evaluated in a phase 1 dose-escalation study in patients with imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). The study enrolled 119 patients, with doses ranging from 50 mg to 1200 mg daily and 400 mg to 600 mg twice daily. Common adverse events included myelosuppression, transient indirect hyperbilirubinemia, and rashes. Nilotinib showed significant activity in imatinib-resistant CML, with hematologic and cytogenetic responses in most patients. The maximum tolerated dose was determined to be 600 mg twice daily, with a favorable safety profile. Nilotinib was more potent than imatinib against CML cells in vitro, with higher binding affinity and selectivity for the ABL kinase. It was effective in patients with and without ABL mutations. However, it had limited efficacy in Ph-positive ALL. Nilotinib prolonged the QTcF interval in some patients, necessitating careful monitoring for cardiac events. The study supports the use of nilotinib in imatinib-resistant CML and highlights its potential as a treatment option. The results indicate that nilotinib is active in imatinib-resistant CML and has a favorable safety profile. Further studies are ongoing to evaluate its efficacy in larger patient populations.Nilotinib, a new BCR-ABL tyrosine kinase inhibitor, was evaluated in a phase 1 dose-escalation study in patients with imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). The study enrolled 119 patients, with doses ranging from 50 mg to 1200 mg daily and 400 mg to 600 mg twice daily. Common adverse events included myelosuppression, transient indirect hyperbilirubinemia, and rashes. Nilotinib showed significant activity in imatinib-resistant CML, with hematologic and cytogenetic responses in most patients. The maximum tolerated dose was determined to be 600 mg twice daily, with a favorable safety profile. Nilotinib was more potent than imatinib against CML cells in vitro, with higher binding affinity and selectivity for the ABL kinase. It was effective in patients with and without ABL mutations. However, it had limited efficacy in Ph-positive ALL. Nilotinib prolonged the QTcF interval in some patients, necessitating careful monitoring for cardiac events. The study supports the use of nilotinib in imatinib-resistant CML and highlights its potential as a treatment option. The results indicate that nilotinib is active in imatinib-resistant CML and has a favorable safety profile. Further studies are ongoing to evaluate its efficacy in larger patient populations.