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

NCT01743989

Description:

This study aims to assess the optimal duration of nilotinib 300 mg BID consolidation treatment, in order that patients remain in treatment-free remission (≥MR4.0) 12 months after starting the Treatment-Free Remission (TFR) phase of the study. Rationale: CP-CML patients who have received 2 or more calendar years of first-line imatinib treatment, and who have failed to achieve the molecular response threshold for treatment cessation (≥MR4.0) have a 50% greater chance of doing by switching to nilotinib; however the optimal duration of consolidation treatment with nilotinib to ensure the highest rate of patients remaining in ≥MR4.0 after entering the TFR phase is not yet known. This protocol therefore aims to assess the potential impact of a longer duration of consolidation treatment with nilotinib, i.e. 12 months versus 24 months, on molecular relapse rate in the first 12 months of treatment-free remission.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Randomized Phase III Study to Assess the Effect of a Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML.
  • Official Title: A Prospective, Randomized, Open Label, Two Arm Phase III Study to Evaluate Treatment Free Remission (TFR) Rate in Patients With Philadelphia-positive CML After Two Different Durations of Consolidation Treatment With Nilotinib 300mg BID.

Clinical Trial IDs

  • ORG STUDY ID: CAMN107AIC05
  • SECONDARY ID: 2012-005124-15
  • NCT ID: NCT01743989

Conditions

  • Leukemia, Myeloid, Ph1-Positive

Interventions

DrugSynonymsArms
Nilotinibarm 1

Purpose

This study aims to assess the optimal duration of nilotinib 300 mg BID consolidation treatment, in order that patients remain in treatment-free remission (≥MR4.0) 12 months after starting the Treatment-Free Remission (TFR) phase of the study. Rationale: CP-CML patients who have received 2 or more calendar years of first-line imatinib treatment, and who have failed to achieve the molecular response threshold for treatment cessation (≥MR4.0) have a 50% greater chance of doing by switching to nilotinib; however the optimal duration of consolidation treatment with nilotinib to ensure the highest rate of patients remaining in ≥MR4.0 after entering the TFR phase is not yet known. This protocol therefore aims to assess the potential impact of a longer duration of consolidation treatment with nilotinib, i.e. 12 months versus 24 months, on molecular relapse rate in the first 12 months of treatment-free remission.

Trial Arms

NameTypeDescriptionInterventions
arm 1Active Comparator12 months of nilotinib consolidation (arm 1) plus 36 months of TFR phase
  • Nilotinib
arm 2Active Comparator24 months of nilotinib consolidation plus 24 months of TFR phase
  • Nilotinib

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;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:optimal duration of consolidation treatment with nilotinib 300 mg BID to ensure the highest rate of patients remaining in ≥MR4.0 12months after entering the TFR phase.
Time Frame:48 months
Safety Issue:
Description:the primary endpoint is the number of patients who remain in treatment free remission (≥MR4.0) ,without molecular relapse, at the end of 12 months in the TFR phase of the study, in the nilotinib 12 months consolidation treatment arm (arm 1) versus the nilotinib 24 months consolidation treatment arm (arm 2).

Secondary Outcome Measures

Measure:To evaluate the proportion of patients who are eligible to suspend nilotinib therapy by achieving and maintaining a sustained ≥MR4.0 for at least 12 months during consolidation treatment with nilotinib 300 mg BID
Time Frame:12 months
Safety Issue:
Description:The proportion of patients who have achieved a sustained ≥MR4.0 (defined as having 4 out of 5 quarterly assessments of ≥MR4.0 by a EUTOS standardized laboratory over the last 12 months and the last assessment before randomization is at least MR4.0) during the consolidation treatment phase of the study.
Measure:The kinetics of the molecular response in patients during induction/consolidation treatment with nilotinib 300 mg BID.
Time Frame:24 or 36 months depending on randomized arm
Safety Issue:
Description:The proportion of patients who achieve MR4.0 or MR4.5 on the study at selected time points during the induction/consolidation phase of the study.
Measure:The kinetics of the molecular response in patients during the TFR phase of the study in the two treatment arms.
Time Frame:36months (arm1); 24 months (arm2)
Safety Issue:
Description:The proportion of patients who maintain in MR4.0 or MR4.5 on the study at selected time points during the TFR phase in each one of the two treatment arms
Measure:Progression-free survival (PFS) rate during the TFR phase of the study.
Time Frame:36 months (arm1); 24 months (arm2)
Safety Issue:
Description:PFS defined as progression to AP/BP or death, where the "failure" event is the earliest occurrence of either of these events; Kaplan-Meier (KM) estimation of PFS is measured from the date of start of the nilotinib TFR phase to the date of the earliest failure event. Patients not known to have recurred or died on or before the cut-off date for the KM analysis will have their PFS interval censored at the earlier of the date of their last assessment (cytogenetic, hematology or extramedullary) for patients who are still on study, and at the date of last contact for patients who are in follow-up.
Measure:Treatment -free survival (TFS) during the TFR phase of the study
Time Frame:36 months (arm1); 24 months (arm 2)
Safety Issue:
Description:TFS is defined as lack of any of the following events: loss of MMR, confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BP, or death from any cause;KM estimation of TFS, which is measured from the date of the start of the nilotinib TFR phase to the date of the earliest of the following: loss of MMR, confirmed loss of MR4.0, re-start of nilotinib treatment, progression to AP/BP, or death from any cause.
Measure:Overall survival (OS) rate during of the TFR phase of the study.
Time Frame:36 months (arm1); 24 months (arm2)
Safety Issue:
Description:Overall survival is defined as the time from start of the TFR phase to the time of death due to any cause. For patients without any event on or before the cut-off date, survival time will be censored at the date of their last assessment for patients who are still on study, and at the date of last contact for patients who are in follow-up -
Measure:Safety profile of nilotinib during the induction/consolidation treatment phase, the TFR phase, and during the treatment re-initiation phase.
Time Frame:60 months
Safety Issue:
Description:Descriptive statistics on adverse events, laboratory abnormalities and clinically notable ECG and other safety parameters during the study

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

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