MACS1148: Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT01131325
Collaborator
(none)
3
Enrollment
3
Locations
1
Arm
6.7
Actual Duration (Months)
1
Patient Per Site
0.1
Patients Per Site Per Month

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
3 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-center, Single Arm Study of Nilotinib in Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Patients With Low Imatinib Trough Plasma Concentrations
Actual Study Start Date :
Oct 21, 2010
Actual Primary Completion Date :
May 12, 2011
Actual Study Completion Date :
May 12, 2011

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nilotinib

Drug: nilotinib
All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours
Other Names:
  • AMN107
  • Tasigna
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. European LeukemiaNet (ELN)-Defined Optimal Responses [up to 2 years]

    2. 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.

    3. 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.

    4. 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.

    5. European LeukemiaNet (ELN)-Defined Suboptimal Events [up to 2 years]

    6. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • Imatinib trough plasma concentration <850 ng/mL

    Exclusion Criteria:
    • Prior documented failure events as defined by ELN guidelines:

    • Loss of CHR, CCyR, or clonal progression/Ph+

    • Less than CHR at 3 months after diagnosis

    • No CyR at 6 months after diagnosis

    • Less than PCyR at 12 months after diagnosis

    • Less than CCyR at 18 months after diagnosis

    • Prior accelerated phase or blast phase CML

    • Previously documented T315I mutation

    • Previous treatment for CML with any other tyrosine kinase inhibitor except for imatinib

    • Patients who had any other treatment for CML (transplant) except interferon +/- ara- C, imatinib, hydroxyurea and/or anagrelide

    • Impaired cardiac function

    • 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.

    • Any other malignancy that is clinically significant or requires active intervention.

    • Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery

    • Treatment with other investigational agents within 30 days of Day 1

    • 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

    • 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

    SiteCityStateCountryPostal Code
    1Comprehensive Cancer Centers of Nevada CCC of Nevada (1)Las VegasNevadaUnited States89109
    2Cancer Center of the High PlainsAmarilloTexasUnited States79106
    3Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (2)DallasTexasUnited States75246

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01131325
    Other Study ID Numbers:
    • CAMN107AUS20
    First Posted:
    May 26, 2010
    Last Update Posted:
    May 20, 2021
    Last Verified:
    Oct 1, 2020

    Study Results

    Participant Flow

    Recruitment DetailsThe study was conducted at 3 centers in the United States.
    Pre-assignment DetailA 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 TitleNilotinib
    Arm/Group DescriptionParticipants 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
    STARTED3
    COMPLETED0
    NOT COMPLETED3

    Baseline Characteristics

    Arm/Group TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Overall Participants3
    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

    1. Primary Outcome
    TitleNumber of Treatment Failure Events up to 2 Years
    DescriptionTreatment 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 Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants0
    2. Secondary Outcome
    TitleEuropean LeukemiaNet (ELN)-Defined Optimal Responses
    Description
    Time Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants0
    3. Secondary Outcome
    TitleLoss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib
    DescriptionComplete 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 Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants0
    4. Secondary Outcome
    TitleDuration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib
    DescriptionDurations 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 Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants0
    5. Secondary Outcome
    TitleEvent-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years
    DescriptionEvent-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 Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants0
    6. Secondary Outcome
    TitleEuropean LeukemiaNet (ELN)-Defined Suboptimal Events
    Description
    Time Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants0
    7. Secondary Outcome
    TitleNumber of Participants Reported Adverse Events
    DescriptionAn 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 FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleNilotinib
    Arm/Group DescriptionParticipants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
    Measure Participants3
    Count of Participants [Participants]
    2
    66.7%

    Adverse Events

    Time Frameup 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 TitleNilotinib
    Arm/Group DescriptionParticipants 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
    Total0/3 (0%)
    Serious Adverse Events
    Nilotinib
    Affected / at Risk (%)# Events
    Total0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Nilotinib
    Affected / at Risk (%)# Events
    Total2/3 (66.7%)
    Blood and lymphatic system disorders
    Thrombocytopenia1/3 (33.3%)
    Neutropenia1/3 (33.3%)
    Gastrointestinal disorders
    Nausea1/3 (33.3%)
    Vomiting1/3 (33.3%)
    General disorders
    Fatigue1/3 (33.3%)
    Mild sweats1/3 (33.3%)
    Infections and infestations
    Sore Throat1/3 (33.3%)
    Musculoskeletal and connective tissue disorders
    Muscle cramps - legs1/3 (33.3%)
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic1/3 (33.3%)
    Skin and subcutaneous tissue disorders
    Rash1/3 (33.3%)
    Pruritus Genital1/3 (33.3%)

    Limitations/Caveats

    The study was terminated early due to slow enrollment.

    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/TitleStudy Director
    OrganizationNovartis Pharmaceuticals
    Phone862-778-8300
    EmailNovartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01131325
    Other Study ID Numbers:
    • CAMN107AUS20
    First Posted:
    May 26, 2010
    Last Update Posted:
    May 20, 2021
    Last Verified:
    Oct 1, 2020