Clinical trial NCT01784068
Conditions: Chronic Myelogenous Leukemia
Keywords: AMN107 Ph+ CML-CP chronic phase nilotinib treatment 2 years treatment MR 4.5 Loss of MR 4 Loss of MMR CML
Sponsor: Novartis Pharmaceuticals
Start date: 2013-03-19; Completion date: 2025-01-23
Enrollment: 215 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The main purpose of the study was to investigate whether nilotinib treatment can be safely suspended with no recurrence of CML in selected patients who responded optimally on this treatment

Detailed description:
The Primary objective of this study was to determine the percentage of patients who were in MMR at 48 weeks after starting the TFR phase (patients who required re-initiation of treatment were considered as non-responders).

Nilotinib treatment consolidation phase (NTCS): Patients who satisfied all inclusion/exclusion criteria were enrolled in the consolidation phase and continued to receive nilotinib for 52 weeks. All patients were treated with the planned nilotinib dose 300 mg BID (or at a reduced dose level of 400 mg QD if required from the perspective of toxicity). In order for patients to be eligible for the TFR phase, they had to fulfill the protocol specific definition of durable MRD. The four last quarterly performed PCR assessments must have fulfilled the following criteria:

* The last assessment was MR4.5 (BCR-ABL ≤ 0.0032% IS)
* No assessment worse than MR4.0 (BCR-ABL \>0.01% IS) and
* No more than two assessments between MR4.0 and MR4.5 (0.0032% IS\<BCR-ABL ≤ 0.01% IS)

Nilotinib TFR phase: Patients who were eligible to enter in the TFR phase after completing the 52 weeks consolidation phase, stopped taking nilotinib on the first day of the TFR phase. Duration of this phase was up to 10 years after the last patient enters in the TFR phase. BCR-ABL levels were monitored every four weeks during the first 48 weeks, every six weeks for the following 48 weeks and every 12 weeks during the last period.

Nilotinib treatment re-initiation (NTRI) phase: If a patient had a loss of MMR (BCR-ABL \>0.1% IS) in the TFR phase, the patient restarted nilotinib treatment. Patients were on nilotinib treatment for up to 10 years after the last patient entered the nilotinib TFR phase. Patients who required re-initiation of nilotinib treatment were monitored for the BCR-ABL level every four weeks for the first 24 weeks and then every 12 weeks thereafter in patients who regained MMR. The frequency of BCR-ABL monitoring in patients not regaining MMR within the first 24 weeks after re-initiation of treatment was at least every 12 weeks or more frequently as clinically indicated.

Arms: arm 1: Patients who received a minimum of 2 years of first line nilotinib treatment and with pre-screen PCR results in ≥ MR4.5 entered the consolidation phase of the study (52 weeks - nilotinib 300 mg BID). Patients with Minimal Residual Disease (MRD) at the end of this phase entered the Treatment-Free Remission (TFR) phase where no treatment was given. Non eligible patients will enter the continuation phase of the study. Patients with MRD at the end of the continuation phase will enter the TFR-2 phase of the study where no treatment is given. Non eligible patients will enter the prolonged continuation phase of the study. If at any time during TFR or TFR-2 the patient loses MMR, nilotinib treatment will be immediately re-initiated (nilotinib 300 mg BID).
Interventions: intervention 1: Nilotinib followed by treatment-free
Intervention descriptions: intervention 1: Nilotinib is being used as commercial available capsules (except in Japan where clinical supplies is used) of 150 mg and 200 mg strength. Treatment occurs during consolidation, continuation, prolonged continuation, re-initiation and re-initiation-2 phases of the study.

Protocol documents: