Sikander Ailawadhi1, Luke P Akard2, Carole B Miller3, Anand Jillella4, Daniel J DeAngelo5, Solveig G Ericson6, Felice Lin6, Ghulam Warsi6, Jerald Radich7. 1. Division of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. 2. Department of Hematology, Indiana Blood and Marrow Transplantation, Indianapolis, IN, USA. 3. Departments of Internal Medicine and Medical Oncology, St. Agnes Hospital, Baltimore, MD, USA. 4. Department of Medicine, Georgia Regents University, Augusta, GA, USA. 5. Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 6. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. 7. Clinical Cancer Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Abstract
BACKGROUND: The phase II, exploratory, open-label Exploring Nilotinib BCR-ABL Effects (ENABL) study [ClinicalTrials.gov identifier: NCT00644878] assessed the impact of switching to nilotinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) who had a suboptimal molecular response with imatinib. METHODS:Patients with CML-CP who had previously achieved a complete cytogenetic response (CCyR), but had a suboptimal molecular response, with frontline imatinib therapy (N = 18) were assigned to receive nilotinib 300 mg twice daily. The primary endpoint was the change in BCR-ABL1 transcript levels from baseline after 12 months; rates of major molecular response (MMR) and safety were also assessed. RESULTS: At 3 months after switching to nilotinib, 10 of 17 (59%) evaluable patients had achieved MMR. At 12 months, 9 of 12 (75%) evaluable patients had achieved MMR, and the median BCR-ABL1 level among all patients remaining in the study was 0.020% on the International Scale (IS), equivalent to a 3.7-log reduction from the standardized IS baseline (primary endpoint). Adverse events (AEs) were typically grade 1/2 and manageable with dose interruptions. A total of three patients experienced serious study drug-related AEs, including pancreatitis, bradycardia, and vertigo. No deaths were reported. CONCLUSIONS: Overall, results from this exploratory study suggest that switching to nilotinib due to suboptimal molecular response with imatinib can result in improved molecular response for patients with CML-CP.
RCT Entities:
BACKGROUND: The phase II, exploratory, open-label Exploring NilotinibBCR-ABL Effects (ENABL) study [ClinicalTrials.gov identifier: NCT00644878] assessed the impact of switching to nilotinib therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP) who had a suboptimal molecular response with imatinib. METHODS:Patients with CML-CP who had previously achieved a complete cytogenetic response (CCyR), but had a suboptimal molecular response, with frontline imatinib therapy (N = 18) were assigned to receive nilotinib 300 mg twice daily. The primary endpoint was the change in BCR-ABL1 transcript levels from baseline after 12 months; rates of major molecular response (MMR) and safety were also assessed. RESULTS: At 3 months after switching to nilotinib, 10 of 17 (59%) evaluable patients had achieved MMR. At 12 months, 9 of 12 (75%) evaluable patients had achieved MMR, and the median BCR-ABL1 level among all patients remaining in the study was 0.020% on the International Scale (IS), equivalent to a 3.7-log reduction from the standardized IS baseline (primary endpoint). Adverse events (AEs) were typically grade 1/2 and manageable with dose interruptions. A total of three patients experienced serious study drug-related AEs, including pancreatitis, bradycardia, and vertigo. No deaths were reported. CONCLUSIONS: Overall, results from this exploratory study suggest that switching to nilotinib due to suboptimal molecular response with imatinib can result in improved molecular response for patients with CML-CP.
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