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The purpose of this study is to investigate whether some patients with excellent responses to chronic myeloid leukaemia (CML) treatment are being overtreated, and can remain well on either a lower dose of treatment or without treatment at all. 

The dose of imatinib (Glivec), nilotinib (Tasigna) or dasatinib (Sprycel) treatment will initially be cut to half the standard dose for 12 months, and then treatment will be stopped completely for a further two years. The trial information will also help to develop a de-escalation and stopping strategy for future newly diagnosed CML patients in the next British national CML study (to be known as SPIRIT3).

This study is currently recruiting participants

Estimated Enrollment ICMJE: 175

Estimated Completion Date: January 2019

Estimated Primary Completion Date : October 2018 (final data collection date for primary outcome measure)

Verified June 2014 by Novartis

Sponsor: Novartis Pharmaceuticals

Collaborators

• Newcastle University
• Imperial College London
• University of Glasgow

Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals)

• First received: January 30, 2013
• Last updated: December 4, 2013
• Last verified: June 2014 by Novartis

Primary Outcome Measures

• Percentage of patients who are in MMR (major molecular response) at 48 weeks after starting the treatment-free remission (TFR) phase [ Time Frame: 48 weeks ] [ Designated as safety issue: No]
• Primary endpoint is the proportion of patients who are in MMR at 48 weeks after starting the TFR phase and is calculated by dividing the number of patients with MMR at 48 weeks after starting the TFR phase with no loss of MMR and no re-initiation of nilotinib therapy in the first 48 weeks after starting the TFR phase by the number of patients entered the TFR phase. Patients who required re-initiation of treatment will be considered as non-responders

Secondary Outcome Measures

• Percentage of patients who are in MR4.5 (BCR-ABL ≤ 0.0032% IS) at 48 weeks after starting the TFR phase [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
• Proportion of patients who are in MR4.5 at 48 weeks after starting the TFR phase is calculated by dividing the number of patients with MR4.5 at 48 weeks after starting the TFR phase with no loss of MR4.5 and no re-initiation of nilotinib therapy in the first 48 weeks after starting the TFR phase by the number of patients who entered the TFR phase.
• Patients who required re-initiation of treatment will be considered as non-responders. MR4.5 = log reductions of the BCR-ABR transcript load in blood as a measurement of deep molecular response of the CML clone to treatment.

Arms Assigned Interventions

• Experimental: Nilotinib followed by treatment-free
• Patients who have received a minimum of 2 years of first line nilotinib treatment and with pre-screen PCR results in ≥ MR4.5 will enter the consolidation phase of the study (52 weeks - nilotinib 300 mg BID). Patients with Minimal Residual Disease (MRD) at the end of this phase will enter the Treatment-Free Remission (TFR) phase where no treatment is 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).

Location countries ICMJE

• United States
• Argentina
• Austria
• Belgium
• Bulgaria
• Colombia
• Denmark
• France
• Germany
• Greece
• Hungary
• Ireland
• Italy
• Japan
• Netherlands
• Poland
• Spain
• Sweden
• United Kingdom