Multicenter Clinical Study on the Safety and Efficacy of Nilotinib Discontinuation in Patients with Chronic Myelogenous Leukemia-Chronic Phase and Complete Molecular Response
- Conditions
- Chronic Myelogenous Leukemia
- Registration Number
- JPRN-UMIN000005904
- Lead Sponsor
- Akita university and the NPO Tohoku Hematology Expert Meeting
- Brief Summary
We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4-78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achiev- ing a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free sur- vival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor- withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete: follow-up complete
- Sex
- All
- Target Recruitment
- 100
Not provided
1) Patients who are participating in any other clinical trial. 2) Patients with the T315I point mutation of BCR-ABL. 3) Patients with a history of hematopoietic stem cell transplantation. 4) Patients with one of the following indicators of cardiovascular dysfunction. i) The QT interval cannot be measured on the ECG ii) Complete left bundle branch block iii) Ventricular pacemaker iv) Congenital QT interval prolongation syndrome or a family history of QT interval prolongation syndrome v) History of or current severe ventricular or atrial tachycardia vi) Clinically significant bradycardia at rest (<50 bpm) vii) History of clinically diagnosed myocardial infarction viii) History of unstable angina within 12 months prior to initiation of the study ix) Other clinically significant cardiovascular complications 5) Patients with another primary malignant tumor. 6) Gastrointestinal dysfunction or diseases that could greatly influence absorption of the study medication. 7) Patients with a history of acute or chronic pancreatitis within 1 year prior to participation to the study. 8) Pregnant women or those with suspected pregnancy. Nursing women and those who plan to become pregnant during the study period. 9) Patients with multiple invasive cancers within 5 years prior to initiation of the study. 10) Patients with other serious or uncontrollable complications. 11) Patients with a psychiatric illness or symptoms that make it difficult to participate in the study. 12) Patients with cognitive dysfunction. 13) Other patients whom the investigator considers to be unsuitable for participation in the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method CMR rate at 1 year after discontinuation of nilotinib treatment in patients who have sustained CMR for 2 years after initiation of the study.
- Secondary Outcome Measures
Name Time Method 1) CMR rate at 2 and 3 years after discontinuation of nilotinib treatment in patients who have sustained CMR for 2 years after initiation of the study. Recurrence-free survival (RFS), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) at 1, 2, and 3 years after the discontinuation of nilotinib. 2) Rate of patients who have sustained CMR for 2 years at 24 months after initiation of the study. 3) Correlation between the time to CMR/MMR and the CMR rate at 1, 2, and 3 years after the discontinuation of treatment. 4) Correlation between the CMR duration prior to the discontinuation of nilotinib treatment and the CMR rate at 1, 2, and 3 years after discontinuation. 5) Exploration of predictors of CMR sustenance during nilotinib treatment.