Trial to Evaluate the Improvement of Chronic Low-grade AEs in Patients With Ph+ CML With Optimal Response to Imatinib When Switched to Nilotinib (MACS1532)
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|ClinicalTrials.gov Identifier: NCT02115386|
Recruitment Status : Completed
First Posted : April 16, 2014
Last Update Posted : March 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Philadelphia Positive (Ph+) Chronic Myeloid Leukemia||Drug: Nilotinib||Phase 3|
Rationale for study was the fact that Nilotinib is approved for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included imatinib (400 mg BID), and for new diagnosed patients with Ph+ CML in CP (300 mg BID). But the majority of CML patients treated with imatinib experience adverse reactions at some time. The most frequently reported drug-related adverse reactions were edema, nausea and vomiting, muscle cramps, musculoskeletal pain, diarrhea and rash. Although the majority of adverse events experienced on imatinib are mild to moderate in grade and most either resolve or diminish over time, low grade adverse events requiring chronic treatment do occur which may adversely impact a patient's quality of life. This study will examine changes in chronic low grade chronic adverse events, measured by CTCAE, when patients are switched from imatinib to nilotinib therapy. So, Primary Objective for this study is to evaluate changes in chronic low grade non-hematological adverse events experienced by patients who have been treated with at least 6 months of imatinib and who have not responded to supportive measures, when they are switched to nilotinib (CTCAE grading system). Primary endpoint is: Changes of non-hematological AE grade at 3 months after switch to nilotinib. Secondary Objectives are: Rate of CCyR after switch to nilotinib (both newly achieved (if absent at baseline) or maintained) at months 1, 3, 6, 12, 18 and 24 after switch to nilotinib; Rate of MMR at 1, 3, 6, 9, 12, 18 and 24 months after switch; Time to and duration of CCyR and MMR after switch until study end; Time to first documented and optimal improvement of the non-hematological adverse event(s) associated with imatinib; Overall nilotinib safety profile; QOL changes after switch to nilotinib and within the study period - measure at baseline (for imatinib) and at 1, 3, 6, 12, and 24 months; Evaluation of patients' experience with switching from imatinib to nilotinib due to low-grade chronic toxicity (diary) Study Design: Open-label, single arm study assessing the changes in chronic low grade adverse events when CML-CP patients are switched from imatinib to nilotinib therapy. Patients must have been treated with starting imatinib dose of 400 mg and at least 300mg QD of imatinib for ≥ 6 months and experience ≤ Grade 2 adverse events which persist ≥ 2 months despite maximal supportive care. Patients have to be optimal responders to imatinib according to LeukemiaNet 2009 criteria at the study entrance.
Adverse events will be graded according to CTCAE guidelines at baseline and will be assessed throughout the trial at each visit. Patients will be treated with nilotinib 300mg BID on study and followed up to 2 years.
Number of patients & centers: 40 patients, 8 centers.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open-label Multicenter Trial to Evaluate the Improvement of Chronic Low-grade Adverse Events Experienced by Patients With Ph+ Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) With Optimal Response to Imatinib When Switched From Imatinib to Nilotinib Treatment|
|Actual Study Start Date :||December 17, 2015|
|Actual Primary Completion Date :||October 31, 2016|
|Actual Study Completion Date :||October 31, 2016|
- improvement of grades of persistent non-hematological AE grade [ Time Frame: at 6 month after switching from imatinib to nilotinib ]To evaluate improvement in chronic low grade non-hematological adverse events, experienced by patients treated with imatinib and persistent despite best supportive measures, when patients are switched from imatinib to nilotinib at 6 months after switch
- improvement of chronic low-grade non-hematologic AEs [ Time Frame: at 3 month after switching from imatinib to nilotinib ]to evaluate improvement of low-grade non-hematologic adverse events, experiences by patients treated with imatinib and persistent despite of best supportive measures after switching to nilotinib therapy
- rate of CCyR [ Time Frame: at months 6,12 and 24 after switching from imatinib to nilotinib ]to evaluate CCyR after switching (both newly achieved or maintained)
- rate of MMR [ Time Frame: at months 1,3, 6, 9, 12, 18 and 24 after switching from imatinib to nilotinib ]to evaluate MMR after switching
- time to and duration of CCyR and MMR [ Time Frame: 24 Months ]to evaluate time to achievement and duration of CCyR and MMR after switching
- time to first improvement of chronic low-grade non-hematologic AEs [ Time Frame: 24 Months ]to evaluate time to first improvement of low-grade non-hematologic adverse events, experiences by patients treated with imatinib and persistent despite of best supportive measures after switching to nilotinib therapy. Optimal improvement is defined as AE grade decreasing to 0.
- summary of biochemistry and hematology AE/SAEs reported [ Time Frame: 24 Months ]to evaluate overall nilotinib safety profile in study
- QOL changes [ Time Frame: at months 1,3,6,12 and 24 after switch to nilotinib ]to evaluate quality of life changes after switching to nilotinib
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02115386
|Novartis Investigative Site|
|Moscow, Russian Federation, 125167|
|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|