This phase 1 study evaluated the safety and efficacy of nilotinib, a new BCR-ABL tyrosine kinase inhibitor, in patients with imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL). Nilotinib was found to have a relatively favorable safety profile, with common adverse events including myelosuppression, transient indirect hyperbilirubinemia, and rashes. The maximum tolerated dose was determined to be 600 mg twice daily. In patients with the blastic phase of disease, 39% had a hematologic response and 27% had a cytogenetic response. Among patients with the accelerated phase, 55% had a hematologic response and 27% had a cytogenetic response. In the chronic phase, 92% of patients achieved a complete hematologic remission, and 35% achieved a complete cytogenetic response. Nilotinib was also active in patients with mutations in the ABL kinase gene that cause imatinib resistance. The study concluded that nilotinib is active in imatinib-resistant CML and has a promising safety profile, warranting further investigation in phase 2 studies.This phase 1 study evaluated the safety and efficacy of nilotinib, a new BCR-ABL tyrosine kinase inhibitor, in patients with imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL). Nilotinib was found to have a relatively favorable safety profile, with common adverse events including myelosuppression, transient indirect hyperbilirubinemia, and rashes. The maximum tolerated dose was determined to be 600 mg twice daily. In patients with the blastic phase of disease, 39% had a hematologic response and 27% had a cytogenetic response. Among patients with the accelerated phase, 55% had a hematologic response and 27% had a cytogenetic response. In the chronic phase, 92% of patients achieved a complete hematologic remission, and 35% achieved a complete cytogenetic response. Nilotinib was also active in patients with mutations in the ABL kinase gene that cause imatinib resistance. The study concluded that nilotinib is active in imatinib-resistant CML and has a promising safety profile, warranting further investigation in phase 2 studies.