A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML.

This study aimed to assess the optimal duration of nilotinib 300 mg twice daily (BID) consolidation treatment in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML), in order that patients remained in treatment-free remission (≥MR4.0) without molecular relapse 12 months after starting the Treatment-Free Remission (TFR) phase.

This was a prospective, randomized, open-label, multicenter Phase III study. The study design was made up of 3 phases:

* Nilotinib induction phase: 12 months
* Nilotinib consolidation phase: 12 or 24 months, depending on randomization
* Nilotinib treatment-free remission (TFR) phase: 24 or 36 months, depending on randomization.

Subjects were enrolled into the study and were treated with nilotinib 300mg twice daily (BID) for 24 months, during the induction (12 months) and consolidation (12 months) phases. At the end of the first 24 months of treatment, participants achieving a sustained molecular response (defined as ≥ MR4.0, in 4 out of 5 real-time quantitative polymerase chain reaction (RQ-PCR) assessments, including the last assessment, in the last 12 months) were randomized on a 1:1 basis to either:

1. suspend nilotinib treatment immediately and enter the TFR phase for 36 months (Nilotinib 24-month treatment arm), or
2. continue nilotinib treatment for a further 12 months (post-randomization consolidation phase), then suspend treatment and enter the TFR phase for 24 months (Nilotinib 36-month treatment arm).

Participants not achieving a sustained molecular response at 24 months from treatment start were not eligible for randomization and were treated at the discretion of the investigator according to standard practice. Information on survival, stem cell transplantation, and status of the patient's disease was collected until death or until 5 years from study entry, whichever came first. Additionally, for Nilotinib 36-month treatment arm, participants who did not achieve a sustained molecular response at 36 months from treatment start, discontinued from the study and were treated according to standard practice and followed up until death or until 5 years from study entry, whichever came first.

Participants relapsing during the TFR phase entered the nilotinib re-treatment phase of the study, and were re-treated with the same dose of nilotinib as they were on before the TFR phase. These patients remained on study until the completion of the 5-year study period unless prematurely withdrawn and discontinued from the study for any reason specified in the Protocol.

Eligibility Criteria:
Key Inclusion Criteria:

* Confirmed diagnosis of chronic phase Ph+ CML
* Previous first-line treatment with imatinib for a minimum of 2 years;
* Patient in complete cytogenetic response;

Key Exclusion Criteria:

* Previous achievement of MR4.0 at study entry;
* Previous treatment with other target cells inhibitors other than imatinib;
* Patients with any history of detectable atypical Leukemia transcripts or patients with detectable atypical leukemia transcripts at screening;
* Previous anticancer agents for Chronic myeloid leukemia other than imatinib except for cytoreduction;
* Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol;
* History of other active malignancies within the 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively;
* Patients who have not recovered from prior surgery;
* Treatment with other investigational agents within 4 weeks of Day 1;
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug

Other inclusion/exclusion criteria might apply.