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A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (ENESTnd)

Primary Purpose

Myelogenous Leukemia, Chronic

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
nilotinib
imatinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelogenous Leukemia, Chronic focused on measuring leukemia, bone marrow, leukemia symptoms, lukemia, cml, complete blood count, lymphocyte, blood cancer, leukocytes, chronic leukemia, bone marrow biopsy, leukemia research, leukemia cells, bone marrow disease, chronic myeloid leukemia, blood cancer symptoms, white blood cell diseases, chronic myelogenous leukemia, leukemia treatment, leukemia facts, leucemia, facts about leukemia, myelogenous leukemia, newly diagnosed CML, newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion criteria:

  • Chronic myelogenous leukemia in chronic phase patients within the first 6 months of diagnosis.
  • Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of Philadelphia chromosome of (9:22) translocations

Key Exclusion criteria:

  • Previously documented T315I mutation
  • Treatment with a tyrosine kinase inhibitor prior to study entry is not allowed except for no more than 2 weeks in duration of imatinib
  • Any medical treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
  • Impaired cardiac function.
  • Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
  • Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
  • Currently receiving treatment with any medications that have the potential to prolong the QT interval.

Sites / Locations

  • University of California at Los Angeles Dept. of Hematology Clinic
  • Kaiser Permanente - California Southern Dept of Kaiser South 3
  • Kaiser Permanente - California Northern Vallejo Med Center/Med Offices
  • Kaiser Permanente - California Northern Kaiser Med
  • Rocky Mountain Cancer Centers RMCC - Colorado Springs
  • Florida Cancer Specialists Dept. FloridaCancerSpecialists
  • Advanced Medical Specialties Research Dept.
  • Cancer Centers of Florida PA Cancer Centers of FL
  • Florida Retina Institute Flordia Cancer Affilates
  • University of Chicago Section of Hematology/Oncology
  • Indiana Blood and Marrow Institute Dept. of Indiana Blood&Marrow
  • University of Iowa Hospitals and Clinics Dept.of U of Iowa Hosp&Clinics
  • Kansas City Cancer Center KCCC Business Office
  • LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
  • Michigan State University / Breslin Cancer Center Breslin Cancer Center
  • Missouri Cancer Associates Dept. of Boone Hospital Center
  • Hematology Oncology Consultants, Inc. Deptof Hem. Onc.Consunsultants
  • Hackensack University Medical Center Department of Research
  • Memorial Sloan Kettering Cancer Center Clinical Trials Office
  • University of North Carolina UNC Lineberger Cancer Center
  • Wake Forest University Health Sciences Dept. of Industry Research
  • University of Cincinnati / Barrett Cancer Center Dept.of Internal Med.
  • Cleveland Clinic Foundation CCF
  • Northwest Cancer Specialists Compass Oncology -BKM
  • Cancer Centers of the Carolinas CC of C -Eastside
  • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
  • Tennessee Oncology Dept. of Centennial Medical
  • Texas Cancer Center ( Medical City Dallas Hospital)
  • Cancer Care Centers of South Texas HOAST CCC of So.TX- Medical Center
  • Tyler Cancer Center
  • Utah Cancer Specialists
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

nilotinib 300mg bid (investigating arm)

Nilotinb 400 mg bid (investigating arm)

imatinib 400mg QD (control arm)

Arm Description

Outcomes

Primary Outcome Measures

Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.

Secondary Outcome Measures

Rates of Durable MMR at 24 Months Between All 3 Arms
Durable MMR at 24 months is defined as having MMR both at 12 months and at 24 months, and with no documented loss of MMR between these 12 month and 24 month time points.
Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months
CCyR is defined as 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Patients with no CCyR as the best response by any specific time point, all missing cytogenetic evaluations by that time point or Ph- at baseline are combined as "Nocomplete cytogenetic response".
Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months based on 12-month cut-off interim data.
Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 6 months and beyond up to 120 months based on final data.
Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib
Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib
This is the molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
Time to First MMR
Time to MMR is defined as time from date of randomization to the date of the first documented MMR in nilotinib treatment arms, compared to imatinib in adult patients with Ph+ CML in CP.
Duration of MMR
Duration of MMR for patients with MMR is defined as the time between date of MMR and the earliest of the following: loss of MMR, CML-related death or progression to AP/BC during study treatment The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts
Time to BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% is defined as: date of first BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% - date of randomization +1.
Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts
It is defined as the time from the date of first documented BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% to the earliest of the following: Loss of BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032%, respectively, CML-related death or progression to AP/BC during study treatment. The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
Rate of Hematologic Response
Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
Time to Complete Cytogenic Response (CCyR)
Time to CCyR is defined as the time from the date of randomization to the date of first documented CCyR
Duration of CCyR
Duration of CCyR is defined as the time from date of first documented CCyR to the earliest date of loss of CCyR.
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring in the core or extension study, or during the follow-up period after discontinuation of core or extension study
Event-free Survival (EFS)
Event-free survival is defined as the time from the date of randomization to the date of first occurrence of any of the following: death due to any cause (if death is the primary reason for discontinuation), progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date death. Up to 10 calendar years of follow up from the date when the last patient randomized received the first dose of study drug in all active treatment arms of adult patients with Ph+ CML CP.
Actual Dose-intensity
Actual dose intensity is defined as total dose over time on treatment
Time to Progression to AP/BC
Time to progression to AP/BC is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of CML related death.
Pharmacokinetics: Cmax
Cmax is defined as the maximum serum concentration after dose
Pharmacokinetics: Cmin
Cmin is defined as the minimum serum concentration after dose
Pharmacokinetics: Tmax
Tmax is defined as the sampling time when maximum measured serum concentration occurs
Pharmacokinetics: AUC0-last
AUC0-last is defined as area under concentration-time curve from time zero to the last measurable sample, calculated by log-linear trapezoidal method
Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Rate of CCyR is defined as the percentage of participants in complete cytogenetic response (CCyR). CcyR is defined as 0% of Ph+ metaphases in the bone marrow.
Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Rate of MMR is defined as the percentage pf participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR))
Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
Rate of ≥ 4.5 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension)
This is the percentage of patients with any emergent mutation on extension treatment. The mutation comprised of T315T, less sensitive to nilotinib, unknown and sensitive to nilotinib.

Full Information

First Posted
May 7, 2007
Last Updated
October 23, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00471497
Brief Title
A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Acronym
ENESTnd
Official Title
A Phase III Multi-center, Open-label, Randomized Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
July 31, 2007 (Actual)
Primary Completion Date
September 2, 2009 (Actual)
Study Completion Date
August 21, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP). An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.
Detailed Description
Primary objectives of this study: Compared the efficacy (major molecular response (MMR) rate at 12 months) of nilotinib at 400 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients. Compared the efficacy (MMR rate at 12 months) of nilotinib at 300 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients. The Primary objectives of Extension Phase of the study: - Characterized the safety and tolerability profile of nilotinib 400 mg BID after failure of imatinib or insufficiently responded to nilotinib 300 mg BID therapy and the safety and tolerability profile of imatinib therapy after failure of nilotinib therapy. The study was designed to determine whether the treatment of newly diagnosed, previously untreated Ph+ CML-CP patients with either nilotinib 300 mg bid or 400 mg bid demonstrated improved efficacy compared to imatinib 400 mg qd. The primary efficacy endpoint was the rate of MMR defined as the proportion of patients who achieved ≥ 3 log reduction in BCR-ABL transcripts compared to either the standardized Baseline established in the IRIS trial (International Randomized Interferon versus STI571) (Cortes et al 2005) or to the BCR-ABL ratio ≤ 0.1% by International Scale, as detected by real-time quantitative polymerase chain reaction (RQ-PCR) at 12 months. The key secondary endpoint was to compare the rate of durable MMR between nilotinib 300 mg bid with that of imatinib, and of nilotinib 400 mg bid with that of imatinib at 24 months. This report presents the final results of efficacy and safety at the LPLV (21-Aug-2019). The main data analysis was done at the time when all patients completed 12 cycles of treatment (or discontinued earlier). There were two primary comparisons at this time point: the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg, and the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg. Comparisons were done sequentially, i.e. the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg was to be compared first; if it was significant at 5% level, the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg was to be compared. The study had a 90% power to detect a 15% difference between the nilotinib 400 mg arm versus imatinib 400 mg arm assuming that the MMR rate of imatinib is 40% and the MMR rate of nilotinib is 55%. The study also had a 90% power to detect a 15% difference between the nilotinib 300 mg and the imatinib 400 mg arms, if the comparison between the nilotinib 400 mg and the imatinib 400 mg was significant. The second main data analysis was done at the time when all patients completed 24 cycles of treatment (or discontinued earlier). There were two key comparisons at this time point: the rate of durable MMR at 24 months of the nilotinib 400 mg versus the imatinib 400 mg, and the rate of durable MMR at 24 months of the nilotinib 300 mg versus the imatinib 400 mg. In order to control the overall type I error rate at or below 5%, only when the corresponding comparison on the primary efficacy endpoint(s) was (were) significant, the key secondary comparison(s) of the respective nilotinib doses (400 mg bid and/or 300 mg bid) versus imatinib 400 mg qd were tested at two-sided 5% significance level. Patients participating after demonstrating suboptimal response/treatment failure to their assigned study treatment in the core study were offered the option to continue in the extension study and to receive imatinib 400 mg bid (option available only until protocol amendment 7) or nilotinib therapy at a dose of 400 mg bid.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelogenous Leukemia, Chronic
Keywords
leukemia, bone marrow, leukemia symptoms, lukemia, cml, complete blood count, lymphocyte, blood cancer, leukocytes, chronic leukemia, bone marrow biopsy, leukemia research, leukemia cells, bone marrow disease, chronic myeloid leukemia, blood cancer symptoms, white blood cell diseases, chronic myelogenous leukemia, leukemia treatment, leukemia facts, leucemia, facts about leukemia, myelogenous leukemia, newly diagnosed CML, newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
846 (Actual)

8. Arms, Groups, and Interventions

Arm Title
nilotinib 300mg bid (investigating arm)
Arm Type
Experimental
Arm Title
Nilotinb 400 mg bid (investigating arm)
Arm Type
Experimental
Arm Title
imatinib 400mg QD (control arm)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
nilotinib
Other Intervention Name(s)
AMN107
Intervention Description
Nilotinib was supplied as 50 mg, 150 mg and 200 mg hard gelatin capsules and administered orally at 300 mg BID (twice a day) or 400 mg BID (twice a day)depending on the randomized dose.
Intervention Type
Drug
Intervention Name(s)
imatinib
Other Intervention Name(s)
STI571
Intervention Description
Imatinib was supplied as 100 mg and 400 mg tablets and administered orally at 400 mg QD (once a day).
Primary Outcome Measure Information:
Title
Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation
Description
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
Time Frame
Baseline, 12 months
Title
Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation
Description
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Rates of Durable MMR at 24 Months Between All 3 Arms
Description
Durable MMR at 24 months is defined as having MMR both at 12 months and at 24 months, and with no documented loss of MMR between these 12 month and 24 month time points.
Time Frame
24 months
Title
Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months
Description
CCyR is defined as 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Patients with no CCyR as the best response by any specific time point, all missing cytogenetic evaluations by that time point or Ph- at baseline are combined as "Nocomplete cytogenetic response".
Time Frame
12, 24, 36, 48, 60, 72 months (M)
Title
Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms
Description
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months based on 12-month cut-off interim data.
Time Frame
12 months
Title
Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms
Description
MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 6 months and beyond up to 120 months based on final data.
Time Frame
6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
Title
Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib
Description
Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
Time Frame
at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
Title
Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib
Description
This is the molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
Time Frame
at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months
Title
Time to First MMR
Description
Time to MMR is defined as time from date of randomization to the date of the first documented MMR in nilotinib treatment arms, compared to imatinib in adult patients with Ph+ CML in CP.
Time Frame
up to 84 months
Title
Duration of MMR
Description
Duration of MMR for patients with MMR is defined as the time between date of MMR and the earliest of the following: loss of MMR, CML-related death or progression to AP/BC during study treatment The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
Time Frame
approx. 11 years
Title
Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts
Description
Time to BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% is defined as: date of first BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% - date of randomization +1.
Time Frame
up to 84 months
Title
Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts
Description
It is defined as the time from the date of first documented BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% to the earliest of the following: Loss of BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032%, respectively, CML-related death or progression to AP/BC during study treatment. The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
Time Frame
approx. 11 years
Title
Rate of Hematologic Response
Description
Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
Time Frame
12 months, 24 months, Overall on Core study (approx. 11 years)
Title
Time to Complete Cytogenic Response (CCyR)
Description
Time to CCyR is defined as the time from the date of randomization to the date of first documented CCyR
Time Frame
24 months
Title
Duration of CCyR
Description
Duration of CCyR is defined as the time from date of first documented CCyR to the earliest date of loss of CCyR.
Time Frame
up to 72 months
Title
Progression-free Survival (PFS)
Description
Progression-free survival is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring in the core or extension study, or during the follow-up period after discontinuation of core or extension study
Time Frame
approx. 11 years
Title
Event-free Survival (EFS)
Description
Event-free survival is defined as the time from the date of randomization to the date of first occurrence of any of the following: death due to any cause (if death is the primary reason for discontinuation), progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR
Time Frame
approx. 11 years
Title
Overall Survival (OS)
Description
OS is defined as the time from the date of randomization to the date death. Up to 10 calendar years of follow up from the date when the last patient randomized received the first dose of study drug in all active treatment arms of adult patients with Ph+ CML CP.
Time Frame
approx. 11 years
Title
Actual Dose-intensity
Description
Actual dose intensity is defined as total dose over time on treatment
Time Frame
approx. 11 years
Title
Time to Progression to AP/BC
Description
Time to progression to AP/BC is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of CML related death.
Time Frame
approx. 11 years
Title
Pharmacokinetics: Cmax
Description
Cmax is defined as the maximum serum concentration after dose
Time Frame
any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
Title
Pharmacokinetics: Cmin
Description
Cmin is defined as the minimum serum concentration after dose
Time Frame
any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
Title
Pharmacokinetics: Tmax
Description
Tmax is defined as the sampling time when maximum measured serum concentration occurs
Time Frame
any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
Title
Pharmacokinetics: AUC0-last
Description
AUC0-last is defined as area under concentration-time curve from time zero to the last measurable sample, calculated by log-linear trapezoidal method
Time Frame
any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration
Title
Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Description
Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
Time Frame
Overall for Extension study for approx. 10 years
Title
Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Description
Rate of CCyR is defined as the percentage of participants in complete cytogenetic response (CCyR). CcyR is defined as 0% of Ph+ metaphases in the bone marrow.
Time Frame
Overall for Extension study for approx. 10 years
Title
Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Description
Rate of MMR is defined as the percentage pf participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR))
Time Frame
Overall for Extension study for approx. 10 years
Title
Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Description
Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
Time Frame
Overall for Extension study for approx. 10 years
Title
Rate of ≥ 4.5 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension)
Description
Molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
Time Frame
Overall for Extension study for approx. 10 years
Title
Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension)
Description
This is the percentage of patients with any emergent mutation on extension treatment. The mutation comprised of T315T, less sensitive to nilotinib, unknown and sensitive to nilotinib.
Time Frame
Overall for Extension study for approx. 10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion criteria: Chronic myelogenous leukemia in chronic phase patients within the first 6 months of diagnosis. Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of Philadelphia chromosome of (9:22) translocations Key Exclusion criteria: Previously documented T315I mutation Treatment with a tyrosine kinase inhibitor prior to study entry is not allowed except for no more than 2 weeks in duration of imatinib Any medical treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide Impaired cardiac function. Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection). Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon) Currently receiving treatment with any medications that have the potential to prolong the QT interval.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of California at Los Angeles Dept. of Hematology Clinic
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Kaiser Permanente - California Southern Dept of Kaiser South 3
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Kaiser Permanente - California Northern Vallejo Med Center/Med Offices
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
Kaiser Permanente - California Northern Kaiser Med
City
Vallejo
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Rocky Mountain Cancer Centers RMCC - Colorado Springs
City
Greenwood Village
State/Province
Colorado
Country
United States
Facility Name
Florida Cancer Specialists Dept. FloridaCancerSpecialists
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Advanced Medical Specialties Research Dept.
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Cancer Centers of Florida PA Cancer Centers of FL
City
Ocoee
State/Province
Florida
ZIP/Postal Code
34761
Country
United States
Facility Name
Florida Retina Institute Flordia Cancer Affilates
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
University of Chicago Section of Hematology/Oncology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana Blood and Marrow Institute Dept. of Indiana Blood&Marrow
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
University of Iowa Hospitals and Clinics Dept.of U of Iowa Hosp&Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Kansas City Cancer Center KCCC Business Office
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
Michigan State University / Breslin Cancer Center Breslin Cancer Center
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48824
Country
United States
Facility Name
Missouri Cancer Associates Dept. of Boone Hospital Center
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65201
Country
United States
Facility Name
Hematology Oncology Consultants, Inc. Deptof Hem. Onc.Consunsultants
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63136
Country
United States
Facility Name
Hackensack University Medical Center Department of Research
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Clinical Trials Office
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University of North Carolina UNC Lineberger Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Wake Forest University Health Sciences Dept. of Industry Research
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Cincinnati / Barrett Cancer Center Dept.of Internal Med.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Cleveland Clinic Foundation CCF
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Northwest Cancer Specialists Compass Oncology -BKM
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Cancer Centers of the Carolinas CC of C -Eastside
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Tennessee Oncology Dept. of Centennial Medical
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Texas Cancer Center ( Medical City Dallas Hospital)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Cancer Care Centers of South Texas HOAST CCC of So.TX- Medical Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Tyler Cancer Center
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1221ADC
Country
Argentina
Facility Name
Novartis Investigative Site
City
La Plata
State/Province
Buenos Aires
ZIP/Postal Code
B1902AVG
Country
Argentina
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Novartis Investigative Site
City
Brasilia
State/Province
DF
ZIP/Postal Code
70330-150
Country
Brazil
Facility Name
Novartis Investigative Site
City
Curitiba
State/Province
PR
ZIP/Postal Code
80060-900
Country
Brazil
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
20211-030
Country
Brazil
Facility Name
Novartis Investigative Site
City
Campinas
State/Province
SP
ZIP/Postal Code
13083-970
Country
Brazil
Facility Name
Novartis Investigative Site
City
Jau
State/Province
SP
ZIP/Postal Code
17210-080
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05403 000
Country
Brazil
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
01224-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
01401-901
Country
Brazil
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E3
Country
Canada
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
Novartis Investigative Site
City
Bogota
State/Province
Cundinamarca
ZIP/Postal Code
110111
Country
Colombia
Facility Name
Novartis Investigative Site
City
Bogota
ZIP/Postal Code
110001
Country
Colombia
Facility Name
Novartis Investigative Site
City
Praha 2
State/Province
Czech Republic
ZIP/Postal Code
128 20
Country
Czechia
Facility Name
Novartis Investigative Site
City
Olomouc
State/Province
CZE
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
Novartis Investigative Site
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
Facility Name
Novartis Investigative Site
City
Vejle
ZIP/Postal Code
DK-7100
Country
Denmark
Facility Name
Novartis Investigative Site
City
Cairo
Country
Egypt
Facility Name
Novartis Investigative Site
City
HUS Helsinki
ZIP/Postal Code
FIN-00029
Country
Finland
Facility Name
Novartis Investigative Site
City
Turku
ZIP/Postal Code
FIN-20521
Country
Finland
Facility Name
Novartis Investigative Site
City
Paris Cedex 10
State/Province
Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Novartis Investigative Site
City
Caen
State/Province
Cedex
ZIP/Postal Code
14033
Country
France
Facility Name
Novartis Investigative Site
City
Saint Priest en Jarez
State/Province
Loire
ZIP/Postal Code
42270
Country
France
Facility Name
Novartis Investigative Site
City
Angers Cedex 1
ZIP/Postal Code
49033
Country
France
Facility Name
Novartis Investigative Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Novartis Investigative Site
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Novartis Investigative Site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Novartis Investigative Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Novartis Investigative Site
City
Nantes
ZIP/Postal Code
44035
Country
France
Facility Name
Novartis Investigative Site
City
Nice Cedex
ZIP/Postal Code
06202
Country
France
Facility Name
Novartis Investigative Site
City
Pierre Benite Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
Novartis Investigative Site
City
Poitiers
ZIP/Postal Code
86000
Country
France
Facility Name
Novartis Investigative Site
City
Rennes
ZIP/Postal Code
35019
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Vandoeuvre les Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Novartis Investigative Site
City
Mannheim
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
68305
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Novartis Investigative Site
City
Eisenach
ZIP/Postal Code
99817
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
Novartis Investigative Site
City
Alessandria
State/Province
AL
ZIP/Postal Code
15100
Country
Italy
Facility Name
Novartis Investigative Site
City
Ancona
State/Province
AN
ZIP/Postal Code
60126
Country
Italy
Facility Name
Novartis Investigative Site
City
Bergamo
State/Province
BG
ZIP/Postal Code
24127
Country
Italy
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Catania
State/Province
CT
ZIP/Postal Code
95123
Country
Italy
Facility Name
Novartis Investigative Site
City
Firenze
State/Province
FI
ZIP/Postal Code
50134
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Novartis Investigative Site
City
Pescara
State/Province
PE
ZIP/Postal Code
65124
Country
Italy
Facility Name
Novartis Investigative Site
City
Pisa
State/Province
PI
ZIP/Postal Code
56126
Country
Italy
Facility Name
Novartis Investigative Site
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Novartis Investigative Site
City
Reggio Calabria
State/Province
RC
ZIP/Postal Code
89124
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00133
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00144
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
Facility Name
Novartis Investigative Site
City
Siena
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
Facility Name
Novartis Investigative Site
City
Udine
State/Province
UD
ZIP/Postal Code
33100
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80132
Country
Italy
Facility Name
Novartis Investigative Site
City
Perugia
ZIP/Postal Code
06129
Country
Italy
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
453-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466 8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Maebashi city
State/Province
Gunma
ZIP/Postal Code
371 8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Maebashi
State/Province
Gunma
ZIP/Postal Code
371-0821
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo city
State/Province
Hokkaido
ZIP/Postal Code
060 8648
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
003-0006
Country
Japan
Facility Name
Novartis Investigative Site
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663 8501
Country
Japan
Facility Name
Novartis Investigative Site
City
Tsukuba city
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Novartis Investigative Site
City
Kanazawa-city
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Novartis Investigative Site
City
Kumamoto City
State/Province
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Novartis Investigative Site
City
Tsu-city
State/Province
Mie
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagasaki-city
State/Province
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka Sayama
State/Province
Osaka
ZIP/Postal Code
589 8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita city
State/Province
Osaka
ZIP/Postal Code
565 0871
Country
Japan
Facility Name
Novartis Investigative Site
City
Hidaka-city
State/Province
Saitama
ZIP/Postal Code
350-1298
Country
Japan
Facility Name
Novartis Investigative Site
City
Hamamatsu-city
State/Province
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
Novartis Investigative Site
City
Shimotsuke
State/Province
Tochigi
ZIP/Postal Code
329-0498
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113 8655
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8519
Country
Japan
Facility Name
Novartis Investigative Site
City
Chuo ku
State/Province
Tokyo
ZIP/Postal Code
104 0045
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinagawa ku
State/Province
Tokyo
ZIP/Postal Code
141 8625
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160 8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Novartis Investigative Site
City
Akita
ZIP/Postal Code
010-8543
Country
Japan
Facility Name
Novartis Investigative Site
City
Chiba
ZIP/Postal Code
260 8677
Country
Japan
Facility Name
Novartis Investigative Site
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Novartis Investigative Site
City
Niigata
ZIP/Postal Code
951 8520
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Novartis Investigative Site
City
Saitama
ZIP/Postal Code
330 8503
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Seocho Gu
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Jeollanam-do
ZIP/Postal Code
519763
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Taegu
ZIP/Postal Code
41944
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Selangor
ZIP/Postal Code
68000
Country
Malaysia
Facility Name
Novartis Investigative Site
City
Mexico
State/Province
Distrito Federal
ZIP/Postal Code
06726
Country
Mexico
Facility Name
Novartis Investigative Site
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Oslo
ZIP/Postal Code
NO-0310
Country
Norway
Facility Name
Novartis Investigative Site
City
Trondheim
ZIP/Postal Code
7006
Country
Norway
Facility Name
Novartis Investigative Site
City
Katowice
ZIP/Postal Code
40032
Country
Poland
Facility Name
Novartis Investigative Site
City
Lublin
ZIP/Postal Code
20-081
Country
Poland
Facility Name
Novartis Investigative Site
City
Rzeszow
ZIP/Postal Code
35 055
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Novartis Investigative Site
City
Wroclaw
ZIP/Postal Code
50-367
Country
Poland
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Novosibirsk
ZIP/Postal Code
630051
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Novartis Investigative Site
City
Bratislava
State/Province
Slovak Republic
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Bratislava
ZIP/Postal Code
85107
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Bloemfontein
ZIP/Postal Code
9301
Country
South Africa
Facility Name
Novartis Investigative Site
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
Facility Name
Novartis Investigative Site
City
Parktown
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Novartis Investigative Site
City
Pretoria
ZIP/Postal Code
0001
Country
South Africa
Facility Name
Novartis Investigative Site
City
Pretoria
ZIP/Postal Code
0027
Country
South Africa
Facility Name
Novartis Investigative Site
City
Elche
State/Province
Alicante
ZIP/Postal Code
03203
Country
Spain
Facility Name
Novartis Investigative Site
City
Granada
State/Province
Andalucia
ZIP/Postal Code
18014
Country
Spain
Facility Name
Novartis Investigative Site
City
Malaga
State/Province
Andalucia
ZIP/Postal Code
29010
Country
Spain
Facility Name
Novartis Investigative Site
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Novartis Investigative Site
City
Salamanca
State/Province
Castilla Y Leon
ZIP/Postal Code
37007
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain
Facility Name
Novartis Investigative Site
City
La Coruna
State/Province
Galicia
ZIP/Postal Code
15006
Country
Spain
Facility Name
Novartis Investigative Site
City
Santiago de Compostela
State/Province
Galicia
ZIP/Postal Code
15706
Country
Spain
Facility Name
Novartis Investigative Site
City
Bilbao
State/Province
Pais Vasco
ZIP/Postal Code
48013
Country
Spain
Facility Name
Novartis Investigative Site
City
San Sebastian
State/Province
Pais Vasco
ZIP/Postal Code
20080
Country
Spain
Facility Name
Novartis Investigative Site
City
La Laguna
State/Province
Santa Cruz De Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Novartis Investigative Site
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Novartis Investigative Site
City
Göteborg
ZIP/Postal Code
SE-413 45
Country
Sweden
Facility Name
Novartis Investigative Site
City
Huddinge
ZIP/Postal Code
SE-14186
Country
Sweden
Facility Name
Novartis Investigative Site
City
Lulea
ZIP/Postal Code
SE 971 80
Country
Sweden
Facility Name
Novartis Investigative Site
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Orebro
ZIP/Postal Code
SE-701 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Facility Name
Novartis Investigative Site
City
Sundsvall
ZIP/Postal Code
SE-851 86
Country
Sweden
Facility Name
Novartis Investigative Site
City
Umeå
ZIP/Postal Code
SE-901 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Geneve
ZIP/Postal Code
1205
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Kaohsiung City
ZIP/Postal Code
83301
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taoyuan
ZIP/Postal Code
33305
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Istanbul
State/Province
TUR
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Novartis Investigative Site
City
Glasgow
ZIP/Postal Code
G12 OYN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Caracas
State/Province
Distrito Capital
ZIP/Postal Code
1010
Country
Venezuela

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
24532039
Citation
Hughes TP, Hochhaus A, Kantarjian HM, Cervantes F, Guilhot F, Niederwieser D, le Coutre PD, Rosti G, Ossenkoppele G, Lobo C, Shibayama H, Fan X, Menssen HD, Kemp C, Larson RA, Saglio G. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily. Haematologica. 2014 Jul;99(7):1204-11. doi: 10.3324/haematol.2013.091272. Epub 2014 Feb 14.
Results Reference
derived
PubMed Identifier
24335106
Citation
Hughes TP, Saglio G, Kantarjian HM, Guilhot F, Niederwieser D, Rosti G, Nakaseko C, De Souza CA, Kalaycio ME, Meier S, Fan X, Menssen HD, Larson RA, Hochhaus A. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014 Feb 27;123(9):1353-60. doi: 10.1182/blood-2013-06-510396. Epub 2013 Dec 11.
Results Reference
derived
PubMed Identifier
23502220
Citation
Hochhaus A, Saglio G, Larson RA, Kim DW, Etienne G, Rosti G, De Souza C, Kurokawa M, Kalaycio ME, Hoenekopp A, Fan X, Shou Y, Kantarjian HM, Hughes TP. Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2013 May 2;121(18):3703-8. doi: 10.1182/blood-2012-04-423418. Epub 2013 Mar 15.
Results Reference
derived
PubMed Identifier
23109697
Citation
Branford S, Kim DW, Soverini S, Haque A, Shou Y, Woodman RC, Kantarjian HM, Martinelli G, Radich JP, Saglio G, Hochhaus A, Hughes TP, Muller MC. Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. J Clin Oncol. 2012 Dec 10;30(35):4323-9. doi: 10.1200/JCO.2011.40.5217. Epub 2012 Oct 29.
Results Reference
derived
PubMed Identifier
22207416
Citation
Larson RA, Yin OQ, Hochhaus A, Saglio G, Clark RE, Nakamae H, Gallagher NJ, Demirhan E, Hughes TP, Kantarjian HM, le Coutre PD. Population pharmacokinetic and exposure-response analysis of nilotinib in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase. Eur J Clin Pharmacol. 2012 May;68(5):723-33. doi: 10.1007/s00228-011-1200-7. Epub 2011 Dec 30.
Results Reference
derived
PubMed Identifier
21856226
Citation
Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, Goh YT, Rosti G, Nakamae H, Gallagher NJ, Hoenekopp A, Blakesley RE, Larson RA, Hughes TP. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011 Sep;12(9):841-51. doi: 10.1016/S1470-2045(11)70201-7. Epub 2011 Aug 17. Erratum In: Lancet Oncol. 2011 Oct;12(11):989.
Results Reference
derived
PubMed Identifier
21467546
Citation
Cortes JE, Hochhaus A, le Coutre PD, Rosti G, Pinilla-Ibarz J, Jabbour E, Gillis K, Woodman RC, Blakesley RE, Giles FJ, Kantarjian HM, Baccarani M. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib. Blood. 2011 May 26;117(21):5600-6. doi: 10.1182/blood-2010-11-318949. Epub 2011 Apr 5.
Results Reference
derived
PubMed Identifier
20525993
Citation
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010 Jun 17;362(24):2251-9. doi: 10.1056/NEJMoa0912614. Epub 2010 Jun 5.
Results Reference
derived

Learn more about this trial

A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

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