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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 (MACS0254)

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ClinicalTrials.gov Identifier: NCT00644878
Recruitment Status : Terminated (Slower than expected enrollment)
First Posted : March 27, 2008
Results First Posted : August 18, 2021
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Chronic Myelogenous Leukemia - Chronic Phase Drug: Nilotinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2008
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012


Arm Intervention/treatment
Experimental: Nilotinib Drug: Nilotinib
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.
Other Names:
  • Tasigna
  • AMN 107




Primary Outcome Measures :
  1. Log Change From Baseline in Breakpoint Cluster Region Gene (BCR) - Abelson Proto-oncogene (ABL) (Bcr-Abl) Transcript Levels [ Time Frame: 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 Outcome Measures :
  1. Number of Participants Who Achieved Major Molecular Response (MMR) [ Time Frame: 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).

  2. Number of Participants Achieved Reduction From a Standardized Baseline Value in Bcr-Abl Transcript Levels up to Month 12 [ Time Frame: 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.

  3. Median Time to Best Molecular Response [ Time Frame: 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.

  4. Duration of Best Molecular Response [ Time Frame: 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

  5. Number of Participants With an Event-free Survival [ Time Frame: 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.

  6. Number of Participants With a Progression-free Survival [ Time Frame: 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.

  7. Number of Participants With an Overall Survival [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00644878


Locations
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United States, California
USC Norris Cancer Center Jane Anne Nohl
Los Angeles, California, United States, 90033
United States, Georgia
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, United States, 30912
United States, Indiana
Indiana Blood and Marrow Institute
Beech Grove, Indiana, United States, 46107
United States, Iowa
University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic
Iowa City, Iowa, United States, 52242
United States, Louisiana
LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center
New Orleans, Louisiana, United States, 70115
United States, Maryland
St. Agnes Hospital
Baltimore, Maryland, United States, 21229
United States, South Carolina
Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29615
United States, Texas
South Texas Institute of Cancer
Corpus Christi, Texas, United States, 78405
Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr
Houston, Texas, United States, 77030
United States, Utah
Central Utah Clinic Central Utah Clinic (7)
Provo, Utah, United States, 84604
United States, Wisconsin
Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00644878    
Other Study ID Numbers: CAMN107AUS09
First Posted: March 27, 2008    Key Record Dates
Results First Posted: August 18, 2021
Last Update Posted: August 18, 2021
Last Verified: July 2021
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
leukemia
chronic myelogenous leukemia
chronic phase
molecular response
nilotinib
ENABL
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes