Chronic Myelogenous Leukemia - Chronic Phase
Conditions
Keywords
leukemia, chronic myelogenous leukemia, chronic phase, molecular response, nilotinib, ENABL
Brief summary
This exploratory study will evaluate the change in molecular response in chronic myelogenous leukemia - chronic phase patients with a complete cytogenetic response and have a suboptimal molecular response to imatinib
Interventions
DRUGNilotinib
Nilotinib 300 mg is taken by mouth twice a day at 12 hour intervals. Nilotinib is to be taken with water on an empty stomach. No food two hours prior to the dose of nilotinib and for one hour following the dose.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Select Inclusion Criteria: * Male or female patients ≥ 18 years of age with a confirmed diagnosis of Ph+ CML-CP and CCyR * A suboptimal molecular response to imatinib defined as: * Group 1: Treated with 1 year of imatinib, complete cytogenetic response (CCyR) but no major molecular response (MMR) (Bcr-Abl levels \>0.1%IS); * Group 2: No specific duration of imatinib required, achieved CCyR but has \>1 log increase in Bcr-Abl transcript levels * Adequate end organ function * Patients must have had an imatinib washout period of at least 3 days and not to exceed 7 days prior to the first dose of nilotinib. Group 1 patients must have been treated with imatinib for at least 1 year. There was no imatinib treatment duration requirement for Group 2 patients. * For Group 1, patients were eligible for screening if they were treated with an imatinib dose of at least 400mg daily. Dose reduction could have occurred as long as the minimum dose was 300mg daily and the reduction lasted ≤ 28 days. The patient was required to be on 400 mg daily (or a higher dose) of imatinib for at least 6 consecutive months leading up to screening for this study. * For Group 2 patients, dose reduction while on imatinib could have occurred as long as the minimum dose was 300 mg daily, and the reduction lasted ≤28 days. Select
Exclusion criteria
* Prior accelerated phase or blast crisis CML * Patients achieving prior CCyR on imatinib who lost cytogenetic response prior to entering study * Previously documented T315I mutations * Prior therapy with any other tyrosine kinase inhibitor except imatinib * Patients with contraindications to receiving nilotinib, including concomitant medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels | From Baseline up to 12 Months | The change on a logarithmic scale at 12 months from a standardized baseline value (100% on the international scale \[IS\]) in Bcr-Abl transcripts as assessed by peripheral blood Quantitative real-time polymerase chain reaction (RQ-PCR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12 | From Baseline up to 12 Months | Number of participants experiencing either a greater than or equal to (\>or=) 1, \>or= 2, or \>or= 3 log10 reduction in Bcr-Abl transcript levels from Baseline to End of Cycle (EOC) 45 (Day1219 - Day1302) were presented. |
| Median Time to Best Molecular Response | From Start of Study up to End of the Study (up to 41 Months) | The median time to best molecular response, defined as the time (in months) from the date of enrollment to the date when the maximum reduction in Bcr-Abl transcript level was observed. |
| Duration of Best Molecular Response | From Start of Study up to End of the Study (up to 41 Months) | Duration of best molecular response, defined as the time (in months) from the date of best molecular response to a date when an increase in \>1 log10 was observed |
| Number of Participants Who Achieved Major Molecular Response (MMR) | From Baseline up to 12 Months | Major Molecular Response (MMR) value at molecular MD is designated a percentage, which is equivalent to a 3-log reduction from a standardized baseline value from the International Randomized InteYesrferon versus STI571 (IRIS) study or 0.1 percent (%) per International Scale (IS). |
| Number of Participants With a Progression-free Survival | From Start of Study up to End of the Study (up to 41 Months) | Progression-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of progression to Accelerated phase (AP) or Blast crisis (BC) phase, chronic myelogenous leukemia (CML) or death. Participants who did not have an event or dropped out without an event are considered censored at the date of the last observed event. |
| Number of Participants With an Overall Survival | From Start of Study Enrollment up to End of the Study (up to 41 Months) | Overall survival was defined as the number of participants from enrollment to the date of death. |
| Number of Participants With an Event-free Survival | From Start of Study up to End of the Study (up to 41 Months) | Event-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of any of the following: loss of complete hematological response (CHR), loss of Complete cytogenetic response (CCyR), \>1 log increase in Bcr-Abl transcripts from the lowest recorded value, progression to accelerated or blast phase, and death. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 12 centers in United States.
Pre-assignment details
A total of 18 participants was enrolled in this study. Due to slower than expected enrollment, the study was terminated on 31 March 2012.
Participants by arm
| Arm | Count |
|---|---|
| Nilotinib Participants orally received a total of 600 mg dose of Nilotinib as 50-mg and 200-mg hard gelatin capsules BID for 12 cycles (each cycle = 28 days). | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal laboratory value | 3 |
| Overall Study | Adverse Event | 2 |
| Overall Study | Protocol deviation | 2 |
| Overall Study | Treatment duration completed as per protocol | 11 |
Baseline characteristics
| Characteristic | Nilotinib |
|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 12.15 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 14 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels
The change on a logarithmic scale at 12 months from a standardized baseline value (100% on the international scale \[IS\]) in Bcr-Abl transcripts as assessed by peripheral blood Quantitative real-time polymerase chain reaction (RQ-PCR).
Time frame: From Baseline up to 12 Months
Population: The analysis was performed in intent-to-treat (ITT) population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment. Here, number of participants analyzed refer to the number of participants evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nilotinib | Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels | Baseline | 2.229 log change | Standard Deviation 0.6165 |
| Nilotinib | Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels | Month 12 | 3.612 log change | Standard Deviation 0.5689 |
Secondary
Duration of Best Molecular Response
Duration of best molecular response, defined as the time (in months) from the date of best molecular response to a date when an increase in \>1 log10 was observed
Time frame: From Start of Study up to End of the Study (up to 41 Months)
Population: Since only one participant met the criterion of losing response (that is \[i.e.,\] an increase in \> 1 log10 is observed after the occurrence of best molecular response), the analysis was not performed. Hence data was not collected and reported.
Secondary
Median Time to Best Molecular Response
The median time to best molecular response, defined as the time (in months) from the date of enrollment to the date when the maximum reduction in Bcr-Abl transcript level was observed.
Time frame: From Start of Study up to End of the Study (up to 41 Months)
Population: The analysis was performed in ITT population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib | Median Time to Best Molecular Response | 13.8 months |
Secondary
Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12
Number of participants experiencing either a greater than or equal to (\>or=) 1, \>or= 2, or \>or= 3 log10 reduction in Bcr-Abl transcript levels from Baseline to End of Cycle (EOC) 45 (Day1219 - Day1302) were presented.
Time frame: From Baseline up to 12 Months
Population: The analysis was performed in ITT population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment. Here the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib | Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12 | >or=1 log10 reduction | 12 Participants |
| Nilotinib | Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12 | >or= 2 log10 reduction | 12 Participants |
| Nilotinib | Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12 | >or= 3 log10 | 9 Participants |
Secondary
Number of Participants Who Achieved Major Molecular Response (MMR)
Major Molecular Response (MMR) value at molecular MD is designated a percentage, which is equivalent to a 3-log reduction from a standardized baseline value from the International Randomized InteYesrferon versus STI571 (IRIS) study or 0.1 percent (%) per International Scale (IS).
Time frame: From Baseline up to 12 Months
Population: The analysis was performed in ITT population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Nilotinib | Number of Participants Who Achieved Major Molecular Response (MMR) | Baseline | Response: Yes | 0 Participants |
| Nilotinib | Number of Participants Who Achieved Major Molecular Response (MMR) | Baseline | Response: No | 18 Participants |
| Nilotinib | Number of Participants Who Achieved Major Molecular Response (MMR) | Baseline | Response: Missing | 0 Participants |
| Nilotinib | Number of Participants Who Achieved Major Molecular Response (MMR) | Month 12 | Response: Yes | 9 Participants |
| Nilotinib | Number of Participants Who Achieved Major Molecular Response (MMR) | Month 12 | Response: No | 3 Participants |
| Nilotinib | Number of Participants Who Achieved Major Molecular Response (MMR) | Month 12 | Response: Missing | 6 Participants |
Secondary
Number of Participants With an Event-free Survival
Event-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of any of the following: loss of complete hematological response (CHR), loss of Complete cytogenetic response (CCyR), \>1 log increase in Bcr-Abl transcripts from the lowest recorded value, progression to accelerated or blast phase, and death.
Time frame: From Start of Study up to End of the Study (up to 41 Months)
Population: The analysis was performed in ITT population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment. Participants who did not have an event or dropped out without an event are considered censored at the date of the last observed event.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib | Number of Participants With an Event-free Survival | Event | 1 Participants |
| Nilotinib | Number of Participants With an Event-free Survival | Censor | 17 Participants |
Secondary
Number of Participants With an Overall Survival
Overall survival was defined as the number of participants from enrollment to the date of death.
Time frame: From Start of Study Enrollment up to End of the Study (up to 41 Months)
Population: The analysis was performed in ITT population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nilotinib | Number of Participants With an Overall Survival | 18 Participants |
Secondary
Number of Participants With a Progression-free Survival
Progression-free survival was defined as the number of participants from the date of enrollment to the date of first occurrence of progression to Accelerated phase (AP) or Blast crisis (BC) phase, chronic myelogenous leukemia (CML) or death. Participants who did not have an event or dropped out without an event are considered censored at the date of the last observed event.
Time frame: From Start of Study up to End of the Study (up to 41 Months)
Population: The analysis was performed in ITT population, defined as all enrolled participants who received at least 1 dose of study drug and had at least 1 post-baseline assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib | Number of Participants With a Progression-free Survival | Censor | 15 Participants |
| Nilotinib | Number of Participants With a Progression-free Survival | Missing | 3 Participants |