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

Chronic Myelogenous Leukemia - Chronic Phase Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00644878
• Other study ID #: CAMN107AUS09
• Status: Terminated
• Phase: Phase 2
• Start date: October 2008
• Est. completion date: March 2012

Study information

• Verified date: July 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myelogenous Leukemia - Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Philadelphia Chromosome

Intervention

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.

Locations

Country	Name	City	State
United States	Georgia Health Sciences University Dept. of MCG	Augusta	Georgia
United States	St. Agnes Hospital	Baltimore	Maryland
United States	Indiana Blood and Marrow Institute	Beech Grove	Indiana
United States	South Texas Institute of Cancer	Corpus Christi	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Baylor College of Medicine - Breast Care Dan L Duncan Cancer Ctr	Houston	Texas
United States	University of Iowa Hospitals & Clinics Univ of Iowa Hosp & Clinic	Iowa City	Iowa
United States	USC Norris Cancer Center Jane Anne Nohl	Los Angeles	California
United States	Froedert Memorial Lutheran Hospital Dept.ofFroedert Memorial	Milwaukee	Wisconsin
United States	LSU HEALTH SCIENCES CENTER/ LSU SCHOOL OF MEDICINE Feist-Weiller Cancer Center	New Orleans	Louisiana
United States	Central Utah Clinic Central Utah Clinic (7)	Provo	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	From Baseline up to 12 Months
Secondary	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).	From Baseline up to 12 Months
Secondary	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.	From Baseline up to 12 Months
Secondary	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.	From Start of Study up to End of the Study (up to 41 Months)
Secondary	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	From Start of Study up to End of the Study (up to 41 Months)
Secondary	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.	From Start of Study up to End of the Study (up to 41 Months)
Secondary	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.	From Start of Study up to End of the Study (up to 41 Months)
Secondary	Number of Participants With an Overall Survival	Overall survival was defined as the number of participants from enrollment to the date of death.	From Start of Study Enrollment up to End of the Study (up to 41 Months)