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)

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

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

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00644878
• Other Study ID Numbers: CAMN107AUS09
• First Posted: March 27, 2008
• 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:

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