MACS1148: Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
Study Details
Study Description
Brief Summary
This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Nilotinib
|
Drug: nilotinib
All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours
Other Names:
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Outcome Measures
Primary Outcome Measures
- Number of Treatment Failure Events up to 2 Years [up to 2 years]
Treatment failure events from time of study entry in Complete molecular response-Chronic phase (CML-CP) participants with low imatinib trough concentrations less than 850 nanogram per milliliter (<850 ng/mL) treated with nilotinib as defined in European LeukemiaNet (ELN)-guideline.
Secondary Outcome Measures
- European LeukemiaNet (ELN)-Defined Optimal Responses [up to 2 years]
- Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib [up to 2 years]
Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit. Major molecular response is defined as values equal or below 0.1% on the International Scale. Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.
- Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib [up to 2 years]
Durations of major/complete cytogenetic response is defined as the time from the first documentation of the major/ complete response to the first documentation of the disease progression.
- Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years [up to 2 years]
Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest. Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria. Overall survival time is defined as the time from the treatment start to the date of death due to any reason.
- European LeukemiaNet (ELN)-Defined Suboptimal Events [up to 2 years]
- Number of Participants Reported Adverse Events [Up to 2 years]
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Cytogenetically confirmed Ph+ CML-CP Any prior dose of Imatinib
-
Imatinib 400 mg daily for ≥7 consecutive days prior to imatinib trough collection
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Imatinib trough plasma concentration <850 ng/mL
Exclusion Criteria:
-
Prior documented failure events as defined by ELN guidelines:
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Loss of CHR, CCyR, or clonal progression/Ph+
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Less than CHR at 3 months after diagnosis
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No CyR at 6 months after diagnosis
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Less than PCyR at 12 months after diagnosis
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Less than CCyR at 18 months after diagnosis
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Prior accelerated phase or blast phase CML
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Previously documented T315I mutation
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Previous treatment for CML with any other tyrosine kinase inhibitor except for imatinib
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Patients who had any other treatment for CML (transplant) except interferon +/- ara- C, imatinib, hydroxyurea and/or anagrelide
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Impaired cardiac function
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Patients receiving therapy with strong inhibitors of CYP3A4 or medications that prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug.
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Any other malignancy that is clinically significant or requires active intervention.
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Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery
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Treatment with other investigational agents within 30 days of Day 1
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Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of nilotinib
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Sexually active male and female patients taking nilotinib unwilling to use adequate contraception throughout the trial and 3 months following discontinuation of study drug
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Comprehensive Cancer Centers of Nevada CCC of Nevada (1) | Las Vegas | Nevada | United States | 89109 |
2 | Cancer Center of the High Plains | Amarillo | Texas | United States | 79106 |
3 | Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (2) | Dallas | Texas | United States | 75246 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAMN107AUS20
Study Results
Participant Flow
Recruitment Details | The study was conducted at 3 centers in the United States. |
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Pre-assignment Detail | A total of 3 participants were enrolled in the study, of which 1 discontinued the study due to Adverse Event (AE) and 2 participants discontinued as the study got terminated. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 milligram (mg) twice daily (bid) through the mouth (po), every 12 hours in a continuous 28-day cycle up to 2 years. |
Period Title: Overall Study | |
STARTED | 3 |
COMPLETED | 0 |
NOT COMPLETED | 3 |
Baseline Characteristics
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Overall Participants | 3 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
3
100%
|
>=65 years |
0
0%
|
Sex: Female, Male (Count of Participants) | |
Female |
0
0%
|
Male |
3
100%
|
Race/Ethnicity, Customized (Count of Participants) | |
Caucasian |
3
100%
|
Outcome Measures
Title | Number of Treatment Failure Events up to 2 Years |
---|---|
Description | Treatment failure events from time of study entry in Complete molecular response-Chronic phase (CML-CP) participants with low imatinib trough concentrations less than 850 nanogram per milliliter (<850 ng/mL) treated with nilotinib as defined in European LeukemiaNet (ELN)-guideline. |
Time Frame | up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 0 |
Title | European LeukemiaNet (ELN)-Defined Optimal Responses |
---|---|
Description | |
Time Frame | up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 0 |
Title | Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib |
---|---|
Description | Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit. Major molecular response is defined as values equal or below 0.1% on the International Scale. Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene. |
Time Frame | up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 0 |
Title | Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib |
---|---|
Description | Durations of major/complete cytogenetic response is defined as the time from the first documentation of the major/ complete response to the first documentation of the disease progression. |
Time Frame | up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 0 |
Title | Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years |
---|---|
Description | Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest. Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria. Overall survival time is defined as the time from the treatment start to the date of death due to any reason. |
Time Frame | up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 0 |
Title | European LeukemiaNet (ELN)-Defined Suboptimal Events |
---|---|
Description | |
Time Frame | up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study. |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 0 |
Title | Number of Participants Reported Adverse Events |
---|---|
Description | An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. |
Time Frame | Up to 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Nilotinib |
---|---|
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. |
Measure Participants | 3 |
Count of Participants [Participants] |
2
66.7%
|
Adverse Events
Time Frame | up to 2 years | |
---|---|---|
Adverse Event Reporting Description | Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical examination or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. | |
Arm/Group Title | Nilotinib | |
Arm/Group Description | Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years. | |
All Cause Mortality |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 0/3 (0%) | |
Serious Adverse Events |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 0/3 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Nilotinib | ||
Affected / at Risk (%) | # Events | |
Total | 2/3 (66.7%) | |
Blood and lymphatic system disorders | ||
Thrombocytopenia | 1/3 (33.3%) | |
Neutropenia | 1/3 (33.3%) | |
Gastrointestinal disorders | ||
Nausea | 1/3 (33.3%) | |
Vomiting | 1/3 (33.3%) | |
General disorders | ||
Fatigue | 1/3 (33.3%) | |
Mild sweats | 1/3 (33.3%) | |
Infections and infestations | ||
Sore Throat | 1/3 (33.3%) | |
Musculoskeletal and connective tissue disorders | ||
Muscle cramps - legs | 1/3 (33.3%) | |
Respiratory, thoracic and mediastinal disorders | ||
Rhinitis allergic | 1/3 (33.3%) | |
Skin and subcutaneous tissue disorders | ||
Rash | 1/3 (33.3%) | |
Pruritus Genital | 1/3 (33.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 862-778-8300 |
Novartis.email@novartis.com |
- CAMN107AUS20