Philidelphia Positive Chronic Myeloid Leukaemia
Conditions
Keywords
CML, Ph-CML, leukaemia, leukemia, chronic myeloid leukemia, chronic myeloid leukaemia, TKI intolerance, tyrosine kinase inhibitor, tyrosine kinase inhibitor intolerance
Brief summary
The purpose of this Australian study was to assess the efficacy and safety of nilotinib 300mg twice daily in patients with chronic myeloid leukemia chronic phase who were intolerant but responsive to 1st line treatment with imatinib or dasatinib. Eligible patients have been previously treated with imatinib or dasatinib for at least 3 months and are experiencing non-hematologic toxicity whilst having documented responses that meet PBS authority for 1st line treatment of CML without current MR4.5.
Detailed description
The study was planned to enroll 130 patients to achieve the sample size requirement for a meaning full conclusion. Study got terminated with 20 patients because of slow recruitment. Therefore, due to small sample size, the results cannot be considered clinical significant.
Interventions
DRUGNilotinib
Nilotinib 150mg hard gelatin capsules taken orally
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
1. Written informed consent prior to screening procedures 2. Eastern Cooperative Oncology Grou (ECOG) Performance Status of 0, 1, or 2. 3. Patient with diagnosis of Ph+ CML-CP associated with BCR-ABL quantifiable by RQ-PCR (IS). 4. Patient has received a minimum of 3 months of imatinib or dasatinib treatment (any dose) since initial diagnosis with a documented response. 5. Patient is eligible for Pharmaceutical Benefits Scheme (PBS) reimbursed 1st line TKI treatment. 6. Patient has experienced non-hematological Adverse Events (AE(s)) of any grade, which persisted for at least 1 month despite supportive care or recurred at any grade at least once. Patients who, at the Investigator's discretion, require immediate discontinuation due to the severity of the adverse event are also eligible. 7. No other current or planned anti-leukemia therapies. 8. Adequate organ function. 9. Potassium, Magnesium and Total Calcium above Lower limit of normal. 10. life expectancy of more than 12 months in the absence of any intervention Key
Exclusion criteria
1. Prior treatment with nilotinib. 2. Prior Accelerated Phase (AP), Blast Crisis (BC) or allogeneic-transplant (unless the patient received an autologous transplant and was in Chrionic Phase (CP) prior to transplant and never in AP or BC). 3. Patient has documented Molecular Response (MR) 4.5 at the time of study entry 4. Patients with atypical BCR-ABL transcript not quantifiable by standard RQ-PCR. 5. Known impaired cardiac function. 6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug. 7. Pregnant or breast feeding (lactating) women. 8. Women of child-bearing potential unwilling or unable to use highly effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month | Baseline, 96 weeks (24 months) | Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL. |
| Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months | Baseline, 48 weeks (12 months), 96 weeks (24 months) | Molecular Response (MR4.0) rate is defined as the percentage of patients who have achieved a 4-log reduction in BCR-ABL levels at 12 months and 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patients were classified as achieving a 1 log reduction in BCR-ABL. |
| Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months | Baseline, 48 weeks (12 months), 96 weeks (24 months) | Major Molecular Response (MMR) rate is defined as the percentage of patients who have achieved a 3 log reduction in BCR-ABL levels at 12 months and at 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood at the 12 and 24 months following the commencement of nilotinib therapy. MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 \* the baseline Value, the patient will be classified as achieving a 1 log drop. |
| Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months | Baseline, 96 weeks (24 months) | Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. Deep molecular response (MR4.5) rate was defined as the percentage of patients who have achieved a 4.5-log reduction (MR4.5) in BCR-ABL levels during the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL. |
| Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | Baseline, 96 weeks (24 months) | Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression-free Survival (PFS) | 96 weeks (24 months) | PFS was defined as the time from the date of baseline visit to the date of earliest progression-defining event: namely progression (or withdrawal due to progression to blast crisis (BC) or accelerated phase (AP) disease), or death from any cause. Patients who did not progress were censored at earliest of the following: * the date of the 24-month visit; * the date of loss to follow-up; * the date of discontinuation of study treatment for any reason other than progression to BC, or AP disease, or death |
| Time to Event Free Survival (EFS) | 96 weeks (24 months) | EFS was defined as the time from date of baseline visit to the first occurrence of any of the following: Disease progression, treatment failure or death from any cause, whichever was earlier. Patients who did not have an event of interest were censored at earliest of the following: * the date of the 24-month visit; * the date of loss to follow-up; * the date of withdrawal from the study for any reason other than lack of efficacy/progressive disease, tolerance to reduced dose or death |
| Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 | No response corresponds to a BCR-ABL ratio \< 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR). |
| Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Baseline, week 12, 24, 48, 96 | Quality of life was assessed using the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) self-administered questionnaire for adult CML patients. The questionnaire consisted of 13 core questions in part I measuring the severity of symptoms, 6 questions in part 2 assessing the interference of symptoms on daily living. The CML component of the MDASI provided an additional 7 CML-specific symptom items: diarrhea, swelling, rash/skin change, muscle soreness/cramping, bruising/bleeding easily, malaise, and headache. In part I (13 questions) and the CML component (7 questions) each question was scored from 0 to 10 where 0 indicates a symptom is not present and 10 indicate the symptom is as bad as you can imagine. For part 1 the total score can therefore range from 0 to 130 and for CML 0 to 70. Part 2 is also recorded on a 0 to 10 scale, but 0 now indicates that the symptom did not interfere and 10 interfered completely. The total score can range from 0 to 60. |
| Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit | Baseline, week 12 (month 3) | The total number of patients that have showed improvement with respect to CTCAE grades at the time of the 12-week visit are reported. Improved is defined as prior to, or at the time of the 12-week visit, the AE has completely resolved. |
| Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96 | MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR). |
| Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 | MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR). |
| Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 | MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR). |
| Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5) | 96 weeks (24 months) | Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels is measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. The derivation of time to molecular response for patients in the study was measured from the date of first nilotinib use, defined as follows: Days to MR4.5 = date of assessment where BCR-ABL ratio is 0.0032% IS - date of baseline + 1. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nilotinib Nilotinib was administered orally at 300 mg BD at approximately 12 hour intervals which had to be taken without food. The capsules were to be swallowed whole with water and no food should have been consumed for at least 2 hours before and at least 1 hour after the dose was taken. Prior to the first dose of nilotinib, patients were required to have an imatinib or dasatinib washout period of at least 3 days. Therapy with nilotinib was to be continued for up to 24 months while on study. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Patient's/guardian's decision | 1 |
| Overall Study | Study Terminated by Sponsor | 14 |
Baseline characteristics
| Characteristic | Nilotinib |
|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 15.1 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Time frame: Baseline, 96 weeks (24 months)
Population: The full analysis set (FAS) consists of all patients enrolled into the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nilotinib | Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month | 50 Percentage of participants |
Primary
Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. Deep molecular response (MR4.5) rate was defined as the percentage of patients who have achieved a 4.5-log reduction (MR4.5) in BCR-ABL levels during the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Time frame: Baseline, 96 weeks (24 months)
Population: The full analysis set (FAS) consists of all patients enrolled into the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nilotinib | Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months | Achieved MR4.5 | 56.1 months | Standard Deviation 42.06 |
| Nilotinib | Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months | Did not achieve MR4.5 | 45.9 months | Standard Deviation 47.81 |
Primary
Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
Major Molecular Response (MMR) rate is defined as the percentage of patients who have achieved a 3 log reduction in BCR-ABL levels at 12 months and at 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood at the 12 and 24 months following the commencement of nilotinib therapy. MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 \* the baseline Value, the patient will be classified as achieving a 1 log drop.
Time frame: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Population: The full analysis set (FAS) consists of all patients enrolled into the study.Analysis of MMR was undertaken on the subgroup of the FAS that was not at MMR at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months | Within 12 months | 75 Percentage of participants |
| Nilotinib | Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months | Within 24 months | 75 Percentage of participants |
Primary
Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
Molecular Response (MR4.0) rate is defined as the percentage of patients who have achieved a 4-log reduction in BCR-ABL levels at 12 months and 24 months following the commencement of nilotinib therapy. Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patients were classified as achieving a 1 log reduction in BCR-ABL.
Time frame: Baseline, 48 weeks (12 months), 96 weeks (24 months)
Population: The full analysis set (FAS) consists of all patients enrolled into the study. Analysis of MR4.0 was undertaken on the subgroup of the FAS that was not at MR4.0 at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months | Within 12 months | 65 Percentage of participants |
| Nilotinib | Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months | Within 24 months | 71 Percentage of participants |
Primary
Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
Deep Molecular Response (MR4.5) rate is defined as the percentage of patients who have achieved a 4.5 -log reduction in Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels. BCR-ABL levels are measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using RQ-PCR. If a post-baseline value for BCR-ABL is \< 0.1 X the baseline value, the patient were classified as achieving a 1 log reduction in BCR-ABL.
Time frame: Baseline, 96 weeks (24 months)
Population: The full analysis set (FAS) consists of all patients enrolled into the study. 'n' in categories indicates patients achieved or did not achieve MR4.5 during 24 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 not achieved: MR4.0 at baseline | 0 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 achieved : MMR at baseline | 4 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 achieved : MR4.0 at baseline | 1 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 achieved: MR4.5 at baseline | 2 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 not achieved: No response at baseline | 5 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 not achieved: MMR at baseline | 5 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 not achieved: MR4.5 at baseline | 0 Participants |
| Nilotinib | Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months | MR4.5 achieved (n=10): No response at baseline | 3 Participants |
Secondary
Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)
Breakpoint cluster region - Abelson murine leukemia (BCR-ABL) levels is measured in patients by real-time quantitative polymerase chain reaction (RQ-PCR) testing of peripheral blood by the 24 months following the commencement of nilotinib therapy. MR4.5 corresponds to a BCR-ABL ratio 0.0032% IS using RQ-PCR. The derivation of time to molecular response for patients in the study was measured from the date of first nilotinib use, defined as follows: Days to MR4.5 = date of assessment where BCR-ABL ratio is 0.0032% IS - date of baseline + 1.
Time frame: 96 weeks (24 months)
Population: The full analysis set (FAS) consists of all patients enrolled into the study. N represents all patients in FAS who achieved MR4.5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nilotinib | Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5) | 343 days |
Secondary
Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
MMR corresponds to a BCR-ABL ratio 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96
Population: Full analysis set. n = number of patients with evaluable data at the defined time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline : MMR | 45.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 4: MMR | 55.6 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 8: MMR | 36.8 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 12: MMR | 40.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 24: MMR | 31.3 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 36: MMR | 26.7 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 48: MMR | 28.6 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 60: MMR | 12.5 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 72: MMR | 0.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 84: MMR | 0.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 96/End of study: MMR | 33.3 percentage of patients |
Secondary
Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
MR4.0 corresponds to a BCR-ABL ratio 0.01% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 12: MR4.0 | 10.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline : MR4.0 | 5.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 4: MR4.0 | 5.6 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 8: MR4.0 | 15.8 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 24: MR4.0 | 18.8 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 36: MR4.0 | 20.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 48: MR4.0 | 14.3 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 60: MR4.0 | 12.5 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 72: MR4.0 | 60.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 84: MR4.0 | 33.3 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 96/End of study: MR4.0 | 16.7 percentage of patients |
Secondary
Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
MR4.5 corresponds to a BCR-ABL ratio 0.0032% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Population: Full analysis set. n = number of patients with evaluable data at the defined time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline : MR4.5 | 10.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 4: MR4.5 | 5.6 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 8: MR4.5 | 21.1 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 12: MR4.5 | 35.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 24: MR4.5 | 31.3 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 36: MR4.5 | 46.7 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 48: MR4.5 | 50.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 60: MR4.5 | 75.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 72: MR4.5 | 40.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 84: MR4.5 | 66.7 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 96/End of study: MR4.5 | 44.4 percentage of patients |
Secondary
Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
No response corresponds to a BCR-ABL ratio \< 0.1% international scale (IS) using Real-time quantitative polymerase chain reaction (RQ-PCR).
Time frame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
Population: Full analysis set. n = number of patients with evaluable data at the defined time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Baseline : No Response | 40.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 4: No response | 33.3 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 8: No response | 26.3 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 12: No response | 15.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 24: No response | 18.8 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 36: No response | 6.7 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 48: No response | 7.1 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 60: No response | 0.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 72: No response | 0.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 84: No response | 0.0 percentage of patients |
| Nilotinib | Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib | Week 96/End of study: No response | 5.6 percentage of patients |
Secondary
Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
Quality of life was assessed using the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) self-administered questionnaire for adult CML patients. The questionnaire consisted of 13 core questions in part I measuring the severity of symptoms, 6 questions in part 2 assessing the interference of symptoms on daily living. The CML component of the MDASI provided an additional 7 CML-specific symptom items: diarrhea, swelling, rash/skin change, muscle soreness/cramping, bruising/bleeding easily, malaise, and headache. In part I (13 questions) and the CML component (7 questions) each question was scored from 0 to 10 where 0 indicates a symptom is not present and 10 indicate the symptom is as bad as you can imagine. For part 1 the total score can therefore range from 0 to 130 and for CML 0 to 70. Part 2 is also recorded on a 0 to 10 scale, but 0 now indicates that the symptom did not interfere and 10 interfered completely. The total score can range from 0 to 60.
Time frame: Baseline, week 12, 24, 48, 96
Population: The full analysis set (FAS) consists of all patients enrolled into the study. 'n' in the categories represents the number of patients with evaluable data for MDASI part 1/MDASI part 2/CML component at different time points. Week 96 includes end of study results for patients that did not complete the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Baseline: MDASI part 1 | 26.6 units on a scale | Standard Deviation 23.88 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 12: MDASI part 1 | 22.7 units on a scale | Standard Deviation 20.31 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 24: MDASI part 1 | 20.7 units on a scale | Standard Deviation 18.08 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 48: MDASI part 1 | 20.4 units on a scale | Standard Deviation 16.57 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 96: MDASI part 1 | 17.5 units on a scale | Standard Deviation 20.44 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Baseline: MDASI part 2 | 12.4 units on a scale | Standard Deviation 14.17 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 12: MDASI part 2 | 7.8 units on a scale | Standard Deviation 11.92 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 24: MDASI part 2 | 8.2 units on a scale | Standard Deviation 12.2 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 48: MDASI part 2 | 7.6 units on a scale | Standard Deviation 10.53 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 96: MDASI part 2 | 9.9 units on a scale | Standard Deviation 15.59 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Baseline: CMLcomponent | 40.9 units on a scale | Standard Deviation 35.02 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 12: CMLcomponent | 31.5 units on a scale | Standard Deviation 30.1 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 24: CMLcomponent | 30.8 units on a scale | Standard Deviation 28.62 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 48: CMLcomponent | 28.2 units on a scale | Standard Deviation 24.43 |
| Nilotinib | Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) | Week 96 CMLcomponent | 25.4 units on a scale | Standard Deviation 31.06 |
Secondary
Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
The total number of patients that have showed improvement with respect to CTCAE grades at the time of the 12-week visit are reported. Improved is defined as prior to, or at the time of the 12-week visit, the AE has completely resolved.
Time frame: Baseline, week 12 (month 3)
Population: The Safety Set (SS) consisted of all patients in the FAS who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib | Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit | Improved : Yes | 11 Participants |
| Nilotinib | Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit | Improved: No | 9 Participants |
Secondary
Time to Event Free Survival (EFS)
EFS was defined as the time from date of baseline visit to the first occurrence of any of the following: Disease progression, treatment failure or death from any cause, whichever was earlier. Patients who did not have an event of interest were censored at earliest of the following: * the date of the 24-month visit; * the date of loss to follow-up; * the date of withdrawal from the study for any reason other than lack of efficacy/progressive disease, tolerance to reduced dose or death
Time frame: 96 weeks (24 months)
Population: There were no patients in the study who were recorded as experiencing treatment failure.
Secondary
Time to Progression-free Survival (PFS)
PFS was defined as the time from the date of baseline visit to the date of earliest progression-defining event: namely progression (or withdrawal due to progression to blast crisis (BC) or accelerated phase (AP) disease), or death from any cause. Patients who did not progress were censored at earliest of the following: * the date of the 24-month visit; * the date of loss to follow-up; * the date of discontinuation of study treatment for any reason other than progression to BC, or AP disease, or death
Time frame: 96 weeks (24 months)
Population: The FAS consists of all patients enrolled into the study. There were no withdrawals due to progression to BC or AP disease, and there were no recorded deaths during the study.