Back to resultsStudy of Molecular Response in Adult Patients on Nilotinib With Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Ph+ CML) in Chronic Phase and a Suboptimal Molecular Response to Imatinib (MACS0254)
Primary Purpose
Chronic Myelogenous Leukemia - Chronic Phase
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nilotinib
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myelogenous Leukemia - Chronic Phase focused on measuring leukemia, chronic myelogenous leukemia, chronic phase, molecular response, nilotinib, ENABL
Eligibility 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
Sites / Locations
- USC Norris Cancer Center Jane Anne Nohl
- Georgia Health Sciences University Dept. of MCG
- Indiana Blood and Marrow Institute
- University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic
- LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
- St. Agnes Hospital
- Cancer Centers of the Carolinas
- South Texas Institute of Cancer
- Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr
- Central Utah Clinic Central Utah Clinic (7)
- Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nilotinib
Arm Description
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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).
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.
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.
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
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.
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.
Number of Participants With an Overall Survival
Overall survival was defined as the number of participants from enrollment to the date of death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00644878
Brief Title
Study of Molecular Response in Adult Patients on Nilotinib With Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Ph+ CML) in Chronic Phase and a Suboptimal Molecular Response to Imatinib
Acronym
MACS0254
Official Title
A Multi-center, Open-label, Exploratory Study of Bcr-Abl Kinetics in Adult Patients on Nilotinib With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) and a Suboptimal Molecular Response to Imatinib
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Why Stopped
Slower than expected enrollment
Study Start Date
October 2008 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelogenous Leukemia - Chronic Phase
Keywords
leukemia, chronic myelogenous leukemia, chronic phase, molecular response, nilotinib, ENABL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nilotinib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Other Intervention Name(s)
Tasigna, AMN 107
Intervention Description
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.
Primary Outcome Measure Information:
Title
Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels
Description
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
Secondary Outcome Measure Information:
Title
Number of Participants Who Achieved Major Molecular Response (MMR)
Description
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
Title
Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12
Description
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
Title
Median Time to Best Molecular Response
Description
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)
Title
Duration of Best Molecular Response
Description
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)
Title
Number of Participants With an Event-free Survival
Description
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)
Title
Number of Participants With a Progression-free Survival
Description
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)
Title
Number of Participants With an Overall Survival
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
USC Norris Cancer Center Jane Anne Nohl
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Georgia Health Sciences University Dept. of MCG
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Indiana Blood and Marrow Institute
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
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
St. Agnes Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Cancer Centers of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
South Texas Institute of Cancer
City
Corpus Christi
State/Province
Texas
ZIP/Postal Code
78405
Country
United States
Facility Name
Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Central Utah Clinic Central Utah Clinic (7)
City
Provo
State/Province
Utah
ZIP/Postal Code
84604
Country
United States
Facility Name
Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28042454
Citation
Ailawadhi S, Akard LP, Miller CB, Jillella A, DeAngelo DJ, Ericson SG, Lin F, Warsi G, Radich J. Exploratory study on the impact of switching to nilotinib in 18 patients with chronic myeloid leukemia in chronic phase with suboptimal response to imatinib. Ther Adv Hematol. 2017 Jan;8(1):3-12. doi: 10.1177/2040620716678118. Epub 2016 Nov 24.
Results Reference
derived
Learn more about this trial
Study of Molecular Response in Adult Patients on Nilotinib With Philadelphia Chromosome Positive Chronic Myelogenous Leukemia (Ph+ CML) in Chronic Phase and a Suboptimal Molecular Response to Imatinib
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